Review on Molecular Mechanism of Hypertensive Nephropathy

Zhen      Peng; Qiaohong      Xu; Wen      Hu; Yimin      Cheng
Abstract

Hypertension, a prevalent chronic ailment, has the potential to impair kidney function, and thereby resulting in hypertensive nephropathy. The escalating incidence of hypertensive nephropathy attributed to the aging population in urban areas, has emerged as a prominent cause of end-stage renal disease. Nevertheless, the intricate pathogenesis of hypertensive nephropathy poses considerable obstacles in terms of precise clinical diagnosis and treatment. This paper aims to consolidate the research findings on the pathogenesis of hypertensive nephropathy by focusing on the perspective of molecular biology.
[1]
Carey RM, Moran AE, Whelton PK. Treatment of hypertension. JAMA  2022; 328(18): 1849-61.
 [http://dx.doi.org/10.1001/jama.2022.19590] [PMID:  36346411]

[2]
Ahmad FB, Anderson RN. The leading causes of death in the US for 2020. JAMA  2021; 325(18): 1829-30.
 [http://dx.doi.org/10.1001/jama.2021.5469] [PMID:  33787821]

[3]
Martín Giménez VM, Mocayar Marón FJ, García S, et al. Central nervous system, peripheral and hemodynamic effects of nanoformulated anandamide in hypertension. Adv Med Sci  2021; 66(1): 72-80.
 [http://dx.doi.org/10.1016/j.advms.2020.12.003] [PMID:  33388673]

[4]
Lu X, Crowley SD. Inflammation in salt-sensitive hypertension and renal damage. Curr Hypertens Rep  2018; 20(12): 103.
 [http://dx.doi.org/10.1007/s11906-018-0903-x] [PMID:  30377822]

[5]
Ku E, Lee BJ, Wei J, Weir MR. Hypertension in CKD: Core curriculum 2019. Am J Kidney Dis  2019; 74(1): 120-31.
 [http://dx.doi.org/10.1053/j.ajkd.2018.12.044] [PMID:  30898362]

[6]
Zhang C, Booz GW, Yu Q, He X, Wang S, Fan F. Conflicting roles of 20-HETE in hypertension and renal end organ damage. Eur J Pharmacol  2018; 833: 190-200.
 [http://dx.doi.org/10.1016/j.ejphar.2018.06.010] [PMID:  29886242]

[7]
Son M, Oh S, Choi J, Jang JT, Son KH, Byun K. Attenuating effects of dieckol on hypertensive nephropathy in spontaneously hypertensive rats. Int J Mol Sci  2021; 22(8): 4230.
 [http://dx.doi.org/10.3390/ijms22084230] [PMID:  33921823]

[8]
Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol  2018; 71(19): e127-248.
 [http://dx.doi.org/10.1016/j.jacc.2017.11.006] [PMID:  29146535]

[9]
Chen WC, Wu SFV, Sun JH, Tai CY, Lee MC, Chu CH. The mediating role of psychological well-being in the relationship between self-care knowledge and disease self-management in patients with hypertensive nephropathy. Int J Environ Res Public Health  2022; 19(14): 8488.
 [http://dx.doi.org/10.3390/ijerph19148488] [PMID:  35886340]

[10]
Nagase M, Shibata S, Yoshida S, Nagase T, Gotoda T, Fujita T. Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker. Hypertension  2006; 47(6): 1084-93.
 [http://dx.doi.org/10.1161/01.HYP.0000222003.28517.99] [PMID:  16636193]

[11]
Shankland SJ. The podocyte’s response to injury: Role in proteinuria and glomerulosclerosis. Kidney Int  2006; 69(12): 2131-47.
 [http://dx.doi.org/10.1038/sj.ki.5000410] [PMID:  16688120]

[12]
Chen HH, Zhang YX, Lv JL, et al. Role of sirtuins in metabolic disease-related renal injury. Biomed Pharmacother  2023; 161: 114417.
 [http://dx.doi.org/10.1016/j.biopha.2023.114417] [PMID:  36812714]

[13]
Ramchandra R, Xing DT, Matear M, Lambert G, Allen AM, May CN. Neurohumoral interactions contributing to renal vasoconstriction and decreased renal blood flow in heart failure. Am J Physiol Regul Integr Comp Physiol  2019; 317(3): R386-96.
 [http://dx.doi.org/10.1152/ajpregu.00026.2019] [PMID:  31241978]

[14]
Su C, Xue J, Ye C, Chen A. Role of the central renin angiotensin system in hypertension. (review) Int J Mol Med  2021; 47(6): 95.
 [http://dx.doi.org/10.3892/ijmm.2021.4928] [PMID:  33846799]

[15]
Remuzzi A, Sangalli F, Macconi D, et al. Regression of renal disease by Angiotensin II antagonism is caused by regeneration of kidney vasculature. J Am Soc Nephrol  2016; 27(3): 699-705.
 [http://dx.doi.org/10.1681/ASN.2014100971] [PMID:  26116358]

[16]
Ko GJ, Obi Y, Tortorici AR, Kalantar-Zadeh K. Dietary protein intake and chronic kidney disease. Curr Opin Clin Nutr Metab Care  2017; 20(1): 77-85.
 [http://dx.doi.org/10.1097/MCO.0000000000000342] [PMID:  27801685]

[17]
Dhande IS, Doris PA. Pulling the hood off genetic susceptibility to hypertensive renal disease. J Am Soc Nephrol  2020; 31(4): 667-8.
 [http://dx.doi.org/10.1681/ASN.2020020139] [PMID:  32123053]

[18]
Liu L, Wang C, Mi Y, et al. Association of MYH9 polymorphisms with hypertension in patients with chronic kidney disease in China. Kidney Blood Press Res  2016; 41(6): 956-65.
 [http://dx.doi.org/10.1159/000452597] [PMID:  27924804]

[19]
Bostrom MA, Lu L, Chou J, et al. Candidate genes for non-diabetic ESRD in African Americans: A genome-wide association study using pooled DNA. Hum Genet  2010; 128(2): 195-204.
 [http://dx.doi.org/10.1007/s00439-010-0842-3] [PMID:  20532800]

[20]
Friedman DJ, Pollak MR. APOL1 nephropathy: From genetics to clinical applications. Clin J Am Soc Nephrol  2021; 16(2): 294-303.
 [http://dx.doi.org/10.2215/CJN.15161219] [PMID:  32616495]

[21]
Foster MC, Coresh J, Fornage M, et al. APOL1 variants associate with increased risk of CKD among African Americans. J Am Soc Nephrol  2013; 24(9): 1484-91.
 [http://dx.doi.org/10.1681/ASN.2013010113] [PMID:  23766536]

[22]
Parsa A, Kao WHL, Xie D, et al. APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med  2013; 369(23): 2183-96.
 [http://dx.doi.org/10.1056/NEJMoa1310345] [PMID:  24206458]

[23]
Kai JD, Cheng LH, Li BF, et al. MYH9 is a novel cancer stem cell marker and prognostic indicator in esophageal cancer that promotes oncogenesis through the PI3K/AKT/mTOR axis. Cell Biol Int  2022; 46(12): 2085-94.
 [http://dx.doi.org/10.1002/cbin.11894] [PMID:  36030536]

[24]
Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science  2010; 329(5993): 841-5.
 [http://dx.doi.org/10.1126/science.1193032] [PMID:  20647424]

[25]
Rigo D, Orias M. Hypertension and kidney disease progression. Clin Nephrol  2020; 93(1): 103-7.
 [http://dx.doi.org/10.5414/CNP92S118] [PMID:  31549630]

[26]
Mota-Zamorano S, González LM, Robles NR, et al. A custom target next-generation sequencing 70-Gene panel and replication study to identify genetic markers of diabetic kidney disease. Genes  2021; 12(12): 1992.
 [http://dx.doi.org/10.3390/genes12121992] [PMID:  34946941]

[27]
Hayek SS, Koh KH, Grams ME, et al. A tripartite complex of suPAR, APOL1 risk variants and αvβ3 integrin on podocytes mediates chronic kidney disease. Nat Med  2017; 23(8): 945-53.
 [http://dx.doi.org/10.1038/nm.4362] [PMID:  28650456]

[28]
Zhang C, Fang X, Zhang H, et al. Genetic susceptibility of hypertension-induced kidney disease. Physiol Rep  2021; 9(1): e14688.
 [http://dx.doi.org/10.14814/phy2.14688] [PMID:  33377622]

[29]
Owiredu WKBA, Appiah M, Obirikorang C, et al. Association of MYH9-rs3752462 polymorphisms with chronic kidney disease among clinically diagnosed hypertensive patients: A case-control study in a Ghanaian population. Clin Hypertens  2020; 26(1): 15.
 [http://dx.doi.org/10.1186/s40885-020-00148-w] [PMID:  32765897]

[30]
Cyrus C, Al-Mueilo S, Vatte C, et al. Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations. BMC Nephrol  2018; 19(1): 88.
 [http://dx.doi.org/10.1186/s12882-018-0890-9] [PMID:  29665793]

[31]
Bourebaba Y, Mularczyk M, Marycz K, Bourebaba L. Catestatin peptide of chromogranin A as a potential new target for several risk factors management in the course of metabolic syndrome. Biomed Pharmacother  2021; 134: 111113.
 [http://dx.doi.org/10.1016/j.biopha.2020.111113] [PMID:  33341043]

[32]
Pasqua T, Rocca C, Spena A, Angelone T, Cerra MC. Modulation of the coronary tone in the expanding scenario of Chromogranin-A and its derived peptides. Future Med Chem  2019; 11(12): 1501-11.
 [http://dx.doi.org/10.4155/fmc-2018-0585] [PMID:  31298577]

[33]
Muntjewerff EM, Dunkel G, Nicolasen MJT, Mahata SK, van den Bogaart G. Catestatin as a target for treatment of inflammatory diseases. Front Immunol  2018; 9: 2199.
 [http://dx.doi.org/10.3389/fimmu.2018.02199] [PMID:  30337922]

[34]
Garg R, Agarwal A, Katekar R, Dadge S, Yadav S, Gayen JR. Chromogranin A-derived peptides pancreastatin and catestatin: emerging therapeutic target for diabetes. Amino Acids  2023; 55(5): 549-61.
 [http://dx.doi.org/10.1007/s00726-023-03252-x] [PMID:  36914766]

[35]
Zhang K, Mir SA, Hightower CM, et al. Molecular mechanism for hypertensive renal disease: Differential regulation of chromogranin a expression at 3′-untranslated region polymorphism C+87T by MicroRNA-107. J Am Soc Nephrol  2015; 26(8): 1816-25.
 [http://dx.doi.org/10.1681/ASN.2014060537] [PMID:  25392232]

[36]
Melincovici CS, Boşca AB, Şuşman S, et al. Vascular endothelial growth factor (VEGF)-key factor in normal and pathological angiogenesis. Rom J Morphol Embryol  2018; 59(2): 455-67.
 [PMID:  30173249]

[37]
Guise E, Chade AR. VEGF therapy for the kidney: Emerging strategies. Am J Physiol Renal Physiol  2018; 315(4): F747-51.
 [http://dx.doi.org/10.1152/ajprenal.00617.2017] [PMID:  29442546]

[38]
Estrada CC, Maldonado A, Mallipattu SK. Therapeutic inhibition of VEGF signaling and associated nephrotoxicities. J Am Soc Nephrol  2019; 30(2): 187-200.
 [http://dx.doi.org/10.1681/ASN.2018080853] [PMID:  30642877]

[39]
Yang JW, Hutchinson IV, Shah T, Fang J, Min DI. Gene polymorphism of vascular endothelial growth factor −1154 G>A is associated with hypertensive nephropathy in a Hispanic population. Mol Biol Rep  2011; 38(4): 2417-25.
 [http://dx.doi.org/10.1007/s11033-010-0376-8] [PMID:  21080079]

[40]
Nakatani S, Ishimura E, Murase T, et al. Plasma xanthine oxidoreductase activity associated with glycemic control in patients with pre-dialysis chronic kidney disease. Kidney Blood Press Res  2021; 46(4): 475-83.
 [http://dx.doi.org/10.1159/000516610] [PMID:  34082427]

[41]
Db A, Mlgr A, Rag B, et al. Uric acid and salt intake as predictors of incident hypertension in a primary care setting - ScienceDirect. Rev Colomb Cardiol  2020; 27(5): 394-9.

[42]
Camargo LL, Montezano AC, Hussain M, et al. Central role of c-Src in NOX5-mediated redox signalling in vascular smooth muscle cells in human hypertension. Cardiovasc Res  2022; 118(5): 1359-73.
 [http://dx.doi.org/10.1093/cvr/cvab171] [PMID:  34320175]

[43]
Yang J, Kamide K, Kokubo Y, et al. Associations of hypertension and its complications with variations in the xanthine dehydrogenase gene. Hypertens Res  2008; 31(5): 931-40.
 [http://dx.doi.org/10.1291/hypres.31.931] [PMID:  18712049]

[44]
Dalman J, Coleman DM. Nonatherosclerotic renovascular hypertension. Surg Clin North Am  2023; 103(4): 733-43.
 [http://dx.doi.org/10.1016/j.suc.2023.05.007] [PMID:  37455034]

[45]
Mashmoushi A, Wolf MTF. A narrative review of Hyporeninemic hypertension-an indicator for monogenic forms of hypertension. Pediatr Med  2022; 5: 21.
 [http://dx.doi.org/10.21037/pm-21-48] [PMID:  36325202]

[46]
Patel S, Rauf A, Khan H, Abu-Izneid T. Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies. Biomed Pharmacother  2017; 94: 317-25.
 [http://dx.doi.org/10.1016/j.biopha.2017.07.091] [PMID:  28772209]

[47]
Abouleka Y, Mohammedi K, Carpentier C, et al. ACE I/D polymorphism, plasma ACE levels, and long-term kidney outcomes or all-cause death in patients with Type 1 diabetes. Diabetes Care  2021; 44(6): 1377-84.
 [http://dx.doi.org/10.2337/dc20-3036] [PMID:  33827803]

[48]
Sasongko TH, Nagalla S. Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease. Cochrane Database Syst Rev  2021; 12(12): CD009191.
 [PMID:  34932828]

[49]
Susilo H, Pikir BS, Thaha M, et al. The Effect of Angiotensin Converting Enzyme (ACE) I/D polymorphism on atherosclerotic cardiovascular disease and cardiovascular mortality risk in non-hemodialyzed chronic kidney disease: The mediating role of plasma ACE level. Genes  2022; 13(7): 1121.
 [http://dx.doi.org/10.3390/genes13071121] [PMID:  35885904]

[50]
Costantino VV, Gil Lorenzo AF, Bocanegra V, Vallés PG. Molecular mechanisms of hypertensive nephropathy: Renoprotective effect of losartan through Hsp70. Cells  2021; 10(11): 3146.
 [http://dx.doi.org/10.3390/cells10113146] [PMID:  34831368]

[51]
Souček M. Perindopril: A long-term certainty in treating hypertension. Vnitr Lek  2021; 67(2): 119-24.
 [http://dx.doi.org/10.36290/vnl.2021.025] [PMID:  34074111]

[52]
Bekassy Z, Lopatko Fagerström I, Bader M, Karpman D. Crosstalk between the renin-angiotensin, complement and kallikrein-kinin systems in inflammation. Nat Rev Immunol  2022; 22(7): 411-28.
 [http://dx.doi.org/10.1038/s41577-021-00634-8] [PMID:  34759348]

[53]
Girolami JP, Bouby N, Richer-Giudicelli C, Alhenc-Gelas F. Kinins and kinin receptors in cardiovascular and renal diseases. Pharmaceuticals  2021; 14(3): 240.
 [http://dx.doi.org/10.3390/ph14030240] [PMID:  33800422]

[54]
Cao X, Wang M, Li J, et al. Fine particulate matter increases airway hyperresponsiveness through kallikrein-bradykinin pathway. Ecotoxicol Environ Saf  2020; 195: 110491.
 [http://dx.doi.org/10.1016/j.ecoenv.2020.110491] [PMID:  32213367]

[55]
Jozwiak L, Drop A, Buraczynska K, Ksiazek P, Mierzicki P, Buraczynska M. Association of the human bradykinin B2 receptor gene with chronic renal failure. Mol Diagn  2004; 8(3): 157-61.
 [http://dx.doi.org/10.1007/BF03260059] [PMID:  15771553]

[56]
Xu H, Jia J. Single-Cell RNA sequencing of peripheral blood reveals immune cell signatures in Alzheimer’s disease. Front Immunol  2021; 12: 645666.
 [http://dx.doi.org/10.3389/fimmu.2021.645666] [PMID:  34447367]

[57]
Long L, Sun Q. Association of end-stage renal disease with HLA phenotypes and panel reactive antibodies in patients awaiting renal transplantation in Hunan province. J Clin Lab Anal  2022; 36(3): e24251.
 [http://dx.doi.org/10.1002/jcla.24251] [PMID:  35083784]

[58]
Noureen N, Shah FA, Lisec J, et al. Revisiting the association between human leukocyte antigen and end-stage renal disease. PLoS One  2020; 15(9): e0238878.
 [http://dx.doi.org/10.1371/journal.pone.0238878] [PMID:  32915858]

[59]
Noureen N, Zaidi N. Association between human leukocyte antigen (HLA) and end-stage renal disease (ESRD): A meta-analysis. PeerJ  2023; 11: e14792.
 [http://dx.doi.org/10.7717/peerj.14792] [PMID:  36815988]

[60]
Xu S, Yang X, Wang Q, et al. Association between HLB-DRB1 gene polymorphisms and hypertension nephropathy. J Jilin Univ  2012; 38(4): 725-9.

[61]
Mastroianni N, Bettinelli A, Bianchetti M, et al. Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome. Am J Hum Genet  1996; 59(5): 1019-26.
 [PMID:  8900229]

[62]
Lin SH, Cheng NL, Hsu YJ, Halperin ML. Intrafamilial phenotype variability in patients with Gitelman syndrome having the same mutations in their thiazide-sensitive sodium/chloride cotransporter. Am J Kidney Dis  2004; 43(2): 304-12.
 [http://dx.doi.org/10.1053/j.ajkd.2003.10.018] [PMID:  14750096]

[63]
Fulchiero R, Seo-Mayer P. Bartter syndrome and Gitelman syndrome. Pediatr Clin North Am  2019; 66(1): 121-34.
 [http://dx.doi.org/10.1016/j.pcl.2018.08.010] [PMID:  30454738]

[64]
Huang CC, Chung CM, Yang CY, et al. SLC12A3 variation and renal function in Chinese patients with hypertension. Front Med  2022; 9: 863275.
 [http://dx.doi.org/10.3389/fmed.2022.863275] [PMID:  35801212]

[65]
Goldsmith EJ, Rodan AR. Intracellular ion control of WNK signaling. Annu Rev Physiol  2023; 85(1): 383-406.
 [http://dx.doi.org/10.1146/annurev-physiol-031522-080651] [PMID:  36228173]

[66]
Veríssimo F, Jordan P. WNK kinases, a novel protein kinase subfamily in multi-cellular organisms. Oncogene  2001; 20(39): 5562-9.
 [http://dx.doi.org/10.1038/sj.onc.1204726] [PMID:  11571656]

[67]
Chiga M, Rai T, Yang SS, et al. Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone. Kidney Int  2008; 74(11): 1403-9.
 [http://dx.doi.org/10.1038/ki.2008.451] [PMID:  18800028]

[68]
Castañeda-Bueno M, Cervantes-Pérez LG, Vázquez N, et al. Activation of the renal Na+: Cl− cotransporter by angiotensin II is a WNK4-dependent process. Proc Natl Acad Sci USA  2012; 109(20): 7929-34.
 [http://dx.doi.org/10.1073/pnas.1200947109] [PMID:  22550170]

[69]
van der Lubbe N, Lim CH, Fenton RA, et al. Angiotensin II induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter independent of aldosterone. Kidney Int  2011; 79(1): 66-76.
 [http://dx.doi.org/10.1038/ki.2010.290] [PMID:  20720527]

[70]
Furusho T, Sohara E, Mandai S, et al. Renal TNFα activates the WNK phosphorylation cascade and contributes to salt-sensitive hypertension in chronic kidney disease. Kidney Int  2020; 97(4): 713-27.
 [http://dx.doi.org/10.1016/j.kint.2019.11.021] [PMID:  32059997]

[71]
Mutchler SM, Kirabo A, Kleyman TR. Epithelial sodium channel and salt-sensitive hypertension. Hypertension  2021; 77(3): 759-67.
 [http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14481] [PMID:  33486988]

[72]
Hamm LL, Feng Z, Hering-Smith KS. Regulation of sodium transport by ENaC in the kidney. Curr Opin Nephrol Hypertens  2010; 19(1): 98-105.
 [http://dx.doi.org/10.1097/MNH.0b013e328332bda4] [PMID:  19996890]

[73]
Frindt G, Meyerson JR, Satty A, Scandura JM, Palmer LG. Expression of ENaC subunits in epithelia. J Gen Physiol  2022; 154(10): e202213124.
 [http://dx.doi.org/10.1085/jgp.202213124] [PMID:  35939271]

[74]
Ji HL, Nie HG, Chang Y, Lian Q, Liu SL. CPT-cGMP is a new ligand of epithelial sodium channels. Int J Biol Sci  2016; 12(4): 359-66.
 [http://dx.doi.org/10.7150/ijbs.13764] [PMID:  27019621]

[75]
Furman D, Chang J, Lartigue L, et al. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat Med  2017; 23(2): 174-84.
 [http://dx.doi.org/10.1038/nm.4267] [PMID:  28092664]

[76]
Fearon WF, Fearon DT. Inflammation and cardiovascular disease: role of the interleukin-1 receptor antagonist. Circulation  2008; 117(20): 2577-9.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.108.772491] [PMID:  18490534]

[77]
Omi T, Kumada M, Kamesaki T, et al. An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension. Eur J Hum Genet  2006; 14(12): 1295-305.
 [http://dx.doi.org/10.1038/sj.ejhg.5201698] [PMID:  16868559]

[78]
Scambler T, Jarosz-Griffiths HH, Lara-Reyna S, et al. ENaC-mediated sodium influx exacerbates NLRP3-dependent inflammation in cystic fibrosis. eLife  2019; 8: e49248.
 [http://dx.doi.org/10.7554/eLife.49248] [PMID:  31532390]

[79]
Banaszak-Ziemska M, Niedziela M. PAPP-A2 a new key regulator of growth. Endokrynol Pol  2017; 68(6): 682-91.
 [http://dx.doi.org/10.5603/EP.a2017.0060] [PMID:  29238946]

[80]
Conover CA, Boldt HB, Bale LK, et al. Pregnancy-associated plasma protein-A2 (PAPP-A2): Tissue expression and biological consequences of gene knockout in mice. Endocrinology  2011; 152(7): 2837-44.
 [http://dx.doi.org/10.1210/en.2011-0036] [PMID:  21586553]

[81]
Hochane M, van den Berg PR, Fan X, et al. Single-cell transcriptomics reveals gene expression dynamics of human fetal kidney development. PLoS Biol  2019; 17(2): e3000152.
 [http://dx.doi.org/10.1371/journal.pbio.3000152] [PMID:  30789893]

[82]
Wang Y, Jia H, Gao WH, et al. Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults. J Hypertens  2021; 39(9): 1817-25.
 [http://dx.doi.org/10.1097/HJH.0000000000002846] [PMID:  33783375]

[83]
Yu L, Lv JC, Zhou X, Zhu L, Hou P, Zhang H. Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients. Hum Genet  2011; 129(3): 335-44.
 [http://dx.doi.org/10.1007/s00439-010-0927-z] [PMID:  21165652]

[84]
Yu L, Hou P, Lv JC, Liu GP, Zhang H. A novel sodium–glucose co-transporter 2 gene (SGLT2) mutation contributes to the abnormal expression of SGLT2 in renal tissues in familial renal glucosuria. Int Urol Nephrol  2014; 46(11): 2237-8.
 [http://dx.doi.org/10.1007/s11255-014-0755-5] [PMID:  24908283]

[85]
Kim S, Jo CH, Kim GH. Effects of empagliflozin on nondiabetic salt-sensitive hypertension in uninephrectomized rats. Hypertens Res  2019; 42(12): 1905-15.
 [http://dx.doi.org/10.1038/s41440-019-0326-3] [PMID:  31537914]

[86]
Kario K, Hoshide S, Okawara Y, et al. Effect of canagliflozin on nocturnal home blood pressure in Japanese patients with type 2 diabetes mellitus: The SHIFT-J study. J Clin Hypertens  2018; 20(10): 1527-35.
 [http://dx.doi.org/10.1111/jch.13367] [PMID:  30246286]

[87]
Jia H, Bao P, Yao S, et al. Associations of SGLT2 genetic polymorphisms with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults. Hypertens Res  2023; 46(7): 1795-803.
 [http://dx.doi.org/10.1038/s41440-023-01301-2] [PMID:  37160967]

[88]
Gu X, Gu D, He J, et al. Resequencing epithelial sodium channel genes identifies rare variants associated with blood pressure salt-sensitivity: The GenSalt study. Am J Hypertens  2018; 31(2): 205-11.
 [http://dx.doi.org/10.1093/ajh/hpx169] [PMID:  29036630]

[89]
Carey RM, Schoeffel CD, Gildea JJ, et al. Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter. Hypertension  2012; 60(5): 1359-66.
 [http://dx.doi.org/10.1161/HYPERTENSIONAHA.112.196071] [PMID:  22987918]

[90]
Barlassina C, Dal Fiume C, Lanzani C, et al. Common genetic variants and haplotypes in renal CLCNKA gene are associated to salt-sensitive hypertension. Hum Mol Genet  2007; 16(13): 1630-8.
 [http://dx.doi.org/10.1093/hmg/ddm112] [PMID:  17510212]

[91]
Chen Z, Wu H, Wang G, Feng Y. Identification of potential candidate genes for hypertensive nephropathy based on gene expression profile. BMC Nephrol  2016; 17(1): 149.
 [http://dx.doi.org/10.1186/s12882-016-0366-8] [PMID:  27756246]

[92]
Kondža M. Bojić M, Tomić I, Maleš Ž, Rezić V, Ćavar I. Characterization of the CYP3A4 enzyme inhibition potential of selected flavonoids. Molecules  2021; 26(10): 3018.
 [http://dx.doi.org/10.3390/molecules26103018] [PMID:  34069400]

[93]
Jia S, Gao K, Huang P, et al. Interactive effects of glucocorticoids and cytochrome P450 polymorphisms on the plasma trough concentrations of voriconazole. Front Pharmacol  2021; 12: 666296.
 [http://dx.doi.org/10.3389/fphar.2021.666296] [PMID:  34113252]

[94]
Bhatnagar V, Garcia EP, O’Connor DT, et al. CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease. Am J Nephrol  2010; 31(2): 95-103.
 [http://dx.doi.org/10.1159/000258688] [PMID:  19907160]

[95]
Déri MT, Kiss ÁF, Tóth K, et al. End-stage renal disease reduces the expression of drug-metabolizing cytochrome P450s. Pharmacol Rep  2020; 72(6): 1695-705.
 [http://dx.doi.org/10.1007/s43440-020-00127-w] [PMID:  32638224]

[96]
Mota-Zamorano S, Robles NR, González LM, et al. Genetics variants in the epoxygenase pathway of arachidonic metabolism are associated with eicosanoids levels and the risk of diabetic nephropathy. J Clin Med  2021; 10(17): 3980.
 [http://dx.doi.org/10.3390/jcm10173980] [PMID:  34501433]

[97]
Chen X, Cao Y, Wang Z, Zhang D, Tang W. Bioinformatic analysis reveals novel hub genes and pathways associated with hypertensive nephropathy. Nephrology  2019; 24(11): 1103-14.
 [http://dx.doi.org/10.1111/nep.13508] [PMID:  30298691]

[98]
Cong C, Yuan X, Hu Y, Chen W, Wang Y, Tao L. Sinigrin attenuates angiotensin II induced kidney injury by inactivating nuclear factor κB and extracellular signal regulated kinase signaling in vivo and in vitro. Int J Mol Med  2021; 48(2): 161.
 [http://dx.doi.org/10.3892/ijmm.2021.4994] [PMID:  34278443]

[99]
Grynberg K, Ma FY, Nikolic-Paterson DJ. The JNK signaling pathway in renal fifibrosis. Front Physiol  2017; 8: 829.
 [http://dx.doi.org/10.3389/fphys.2017.00829] [PMID:  29114233]

[100]
Liu H, Li X, Xie J, et al. Gypenoside L and Gypenoside LI inhibit proliferation in renal cell carcinoma via regulation of the MAPK and arachidonic acid metabolism pathways. Front Pharmacol  2022; 13: 820639.
 [http://dx.doi.org/10.3389/fphar.2022.820639] [PMID:  35370678]

[101]
Kabei K, Tateishi Y, Nozaki M, et al. Role of hypoxia-inducible factor-1 in the development of renal fibrosis in mouse obstructed kidney: Special references to HIF-1 dependent gene expression of profibrogenic molecules. J Pharmacol Sci  2018; 136(1): 31-8.
 [http://dx.doi.org/10.1016/j.jphs.2017.12.004] [PMID:  29352658]

[102]
Hasan AU, Kittikulsuth W, Yamaguchi F, et al. IBMX protects human proximal tubular epithelial cells from hypoxic stress through suppressing hypoxia-inducible factor-1α expression. Exp Cell Res  2017; 358(2): 343-51.
 [http://dx.doi.org/10.1016/j.yexcr.2017.07.007] [PMID:  28689812]

[103]
You S, Xu J, Wu B, et al. Comprehensive bioinformatics analysis identifies POLR2I as a key gene in the pathogenesis of hypertensive nephropathy. Front Genet  2021; 12: 698570.
 [http://dx.doi.org/10.3389/fgene.2021.698570] [PMID:  34422001]

[104]
Berkyurek AC, Furlan G, Lampersberger L, et al. The RNA polymerase II subunit RPB-9 recruits the integrator complex to terminate Caenorhabditis elegans piRNA transcription. EMBO J  2021; 40(5): e105565.
 [http://dx.doi.org/10.15252/embj.2020105565] [PMID:  33533030]

[105]
Vishnoi A, Rani S. miRNA biogenesis and regulation of diseases: An updated overview. Methods Mol Biol  2023; 2595: 1-12.
 [http://dx.doi.org/10.1007/978-1-0716-2823-2_1] [PMID:  36441451]

[106]
Lu Y, Thavarajah T, Gu W, Cai J, Xu Q. Impact of miRNA in atherosclerosis. Arterioscler Thromb Vasc Biol  2018; 38(9): e159-70.
 [http://dx.doi.org/10.1161/ATVBAHA.118.310227] [PMID:  30354259]

[107]
Henning RJ. Cardiovascular exosomes and microRNAs in cardiovascular physiology and pathophysiology. J Cardiovasc Transl Res  2021; 14(2): 195-212.
 [http://dx.doi.org/10.1007/s12265-020-10040-5] [PMID:  32588374]

[108]
Di Castro S, Scarpino S, Marchitti S, et al. Differential modulation of uncoupling protein 2 in kidneys of stroke-prone spontaneously hypertensive rats under high-salt/low-potassium diet. Hypertension  2013; 61(2): 534-41.
 [http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.00101] [PMID:  23297375]

[109]
Gregory PA, Bracken CP, Bert AG, Goodall GJ. MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle  2008; 7(20): 3112-7.
 [http://dx.doi.org/10.4161/cc.7.20.6851] [PMID:  18927505]

[110]
Bracken CP, Gregory PA, Kolesnikoff N, et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res  2008; 68(19): 7846-54.
 [http://dx.doi.org/10.1158/0008-5472.CAN-08-1942] [PMID:  18829540]

[111]
Kato M, Zhang J, Wang M, et al. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-β-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci USA  2007; 104(9): 3432-7.
 [http://dx.doi.org/10.1073/pnas.0611192104] [PMID:  17360662]

[112]
Wang G, Kwan BCH, Lai FMM, et al. Intrarenal expression of miRNAs in patients with hypertensive nephrosclerosis. Am J Hypertens  2010; 23(1): 78-84.
 [http://dx.doi.org/10.1038/ajh.2009.208] [PMID:  19910931]

[113]
Khalilian S, Abedinlou H, Hussen BM, Imani SZH, Ghafouri-Fard S. The emerging role of miR-20b in human cancer and other disorders: Pathophysiology and therapeutic implications. Front Oncol  2022; 12: 985457.
 [http://dx.doi.org/10.3389/fonc.2022.985457] [PMID:  36582800]

[114]
Steglich A, Hickmann L, Linkermann A, Bornstein S, Hugo C, Todorov VT. Beyond the paradigm: Novel functions of renin-producing cells. Rev Physiol Biochem Pharmacol  2020; 177: 53-81.
 [http://dx.doi.org/10.1007/112_2020_27] [PMID:  32691160]

[115]
Bhushan S, Xiao Z, Gao K, et al. Role and interaction between ACE1, ACE2 and their related genes in cardiovascular disorders. Curr Probl Cardiol  2023; 48(8): 101162.
 [http://dx.doi.org/10.1016/j.cpcardiol.2022.101162] [PMID:  35245599]

[116]
Meng X, Nikolic-Paterson DJ, Lan HY. TGF-β The master regulator of fibrosis. Nat Rev Nephrol  2016; 12(6): 325-38.
 [http://dx.doi.org/10.1038/nrneph.2016.48] [PMID:  27108839]

[117]
Cong C, Yuan X, Hu Y, Chen W, Wang Y, Tao L. Catalpol alleviates ang II-induced renal injury through NF-κB pathway and TGF-β1/Smads pathway. J Cardiovasc Pharmacol  2022; 79(1): e116-21.
 [http://dx.doi.org/10.1097/FJC.0000000000001148] [PMID:  34654783]

[118]
Massagué J. TGFβ signalling in context. Nat Rev Mol Cell Biol  2012; 13(10): 616-30.
 [http://dx.doi.org/10.1038/nrm3434] [PMID:  22992590]

[119]
Zhang J, Cao L, Wang X, et al. The E3 ubiquitin ligase TRIM31 plays a critical role in hypertensive nephropathy by promoting proteasomal degradation of MAP3K7 in the TGF-β1 signaling pathway. Cell Death Differ  2022; 29(3): 556-67.
 [http://dx.doi.org/10.1038/s41418-021-00874-0] [PMID:  34584221]

[120]
Higgins SP, Tang Y, Higgins CE, et al. TGF-β1/p53 signaling in renal fibrogenesis. Cell Signal  2018; 43: 1-10.
 [http://dx.doi.org/10.1016/j.cellsig.2017.11.005] [PMID:  29191563]

[121]
Qin M, Huang S, Zou X, et al. Drug-containing serum of rhubarb-astragalus capsule inhibits the epithelial-mesenchymal transformation of HK-2 by downregulating TGF-β1/p38MAPK/Smad2/3 pathway. J Ethnopharmacol  2021; 280: 114414.
 [http://dx.doi.org/10.1016/j.jep.2021.114414] [PMID:  34314804]

[122]
Xiao H, Li B, Yang X, Yin Q. Interference of TGF-β1/Smad7 signal pathway affects myocardial fibrosis in hypertension. Pak J Pharm Sci  2020; 33(6): 2625-31.
 [PMID:  33867340]

[123]
Hu Y, He J, He L, Xu B, Wang Q. Expression and function of Smad7 in autoimmune and inflammatory diseases. J Mol Med  2021; 99(9): 1209-20.
 [http://dx.doi.org/10.1007/s00109-021-02083-1] [PMID:  34059951]

[124]
Song Y, Wu Z, Zhao P. The protective effects of activating Sirt1/NF-κB pathway for neurological disorders. Rev Neurosci  2022; 33(4): 427-38.
 [http://dx.doi.org/10.1515/revneuro-2021-0118] [PMID:  34757706]

[125]
Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell  2010; 140(6): 805-20.
 [http://dx.doi.org/10.1016/j.cell.2010.01.022] [PMID:  20303872]

[126]
Lin K, Luo W, Yang N, et al. Inhibition of MyD88 attenuates angiotensin II-induced hypertensive kidney disease via regulating renal inflammation. Int Immunopharmacol  2022; 112: 109218.
 [http://dx.doi.org/10.1016/j.intimp.2022.109218] [PMID:  36116148]

[127]
Hu X. li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: From bench to clinic. Signal Transduct Target Ther  2021; 6(1): 402.
 [http://dx.doi.org/10.1038/s41392-021-00791-1] [PMID:  34824210]

[128]
Xu Z, Zou C, Yu W, et al. Inhibition of STAT3 activation mediated by toll-like receptor 4 attenuates angiotensin II-induced renal fibrosis and dysfunction. Br J Pharmacol  2019; 176(14): 2627-41.
 [http://dx.doi.org/10.1111/bph.14686] [PMID:  30958891]

[129]
Santos RAS, Ferreira AJ, Verano-Braga T, Bader M. Angiotensin-converting enzyme 2, angiotensin-(1-7) and Mas: New players of the renin-angiotensin system. J Endocrinol  2013; 216(2): R1-R17.
 [http://dx.doi.org/10.1530/JOE-12-0341] [PMID:  23092879]

[130]
Jiang F, Yang J, Zhang Y, et al. Angiotensin-converting enzyme 2 and angiotensin 1-7: Novel therapeutic targets. Nat Rev Cardiol  2014; 11(7): 413-26.
 [http://dx.doi.org/10.1038/nrcardio.2014.59] [PMID:  24776703]

[131]
Santos RAS, e Silva ACS, Maric C, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci USA  2003; 100(14): 8258-63.
 [http://dx.doi.org/10.1073/pnas.1432869100] [PMID:  12829792]

[132]
Ni J, Yang F, Huang XR, et al. Dual deficiency of angiotensin-converting enzyme-2 and Mas receptor enhances angiotensin II-induced hypertension and hypertensive nephropathy. J Cell Mol Med  2020; 24(22): 13093-103.
 [http://dx.doi.org/10.1111/jcmm.15914] [PMID:  32971570]

[133]
Munir M. TRIM proteins: Another class of viral victims. Sci Signal  2010; 3(118): jc2.
 [http://dx.doi.org/10.1126/scisignal.3118jc2] [PMID:  20407122]

[134]
Yu C, Chen S, Guo Y, Sun C. Oncogenic TRIM31 confers gemcitabine resistance in pancreatic cancer via activating the NF-κB signaling pathway. Theranostics  2018; 8(12): 3224-36.
 [http://dx.doi.org/10.7150/thno.23259] [PMID:  29930725]

[135]
Song H, Liu B, Huai W, et al. The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation by promoting proteasomal degradation of NLRP3. Nat Commun  2016; 7(1): 13727.
 [http://dx.doi.org/10.1038/ncomms13727] [PMID:  27929086]

[136]
Zhang Y, Zhang N, Zou Y, et al. Deacetylation of Septin4 by SIRT2 (Silent Mating Type Information Regulation 2 Homolog-2) mitigates damaging of hypertensive nephropathy. Circ Res  2023; 132(5): 601-24.
 [http://dx.doi.org/10.1161/CIRCRESAHA.122.321591] [PMID:  36786216]

[137]
Xu SB, Xu B, Ma ZH, Huang MQ, Gao ZS, Ni JL. Peptide 17 alleviates early hypertensive renal injury by regulating the Hippo/YAP signalling pathway. Nephrology  2022; 27(8): 712-23.
 [http://dx.doi.org/10.1111/nep.14066] [PMID:  35608936]

[138]
Liu Z, Huang XR, Chen HY, Fung E, Liu J, Lan HY. Deletion of angiotensin-converting enzyme-2 promotes hypertensive nephropathy by targeting Smad7 for Ubiquitin degradation. Hypertension  2017; 70(4): 822-30.
 [http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09600] [PMID:  28808068]
Cite As
Current Pharmaceutical Design

Review on Molecular Mechanism of Hypertensive Nephropathy

Abstract
