Generic placeholder image

Current Molecular Medicine

Author(s): Azadeh Hasanzadeh, Molouk Beiromvand*, Abdollah Rafiei, Mohammad Kazemi, Amin Bahreini and Hossein Khanahmad

DOI: 10.2174/1566524023666230106163928

DownloadDownload PDF Flyer Cite As
Expression of Matrix Metalloproteinases in Human Cystic Echinococcosis

Page: [244 - 251] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: Cystic echinococcosis (CE) is a zoonotic disease caused by the Echinococcus granulosus senso lato (E. granulosus s.l.) larval stages. Parasitederived products have been shown to regulate host matrix metalloproteinases (MMPs), contributing to CE pathogenesis and progressive liver fibrosis in intermediate hosts. The current study aimed to investigate the potential role of MMP1, 7, 8, and 13 in E. granulosus s.l-induced liver fibrosis.

Methods: Thirty CE patients with active, transitional, or inactive hydatid cysts were enrolled in this study to determine the inductive effects of E. granulosus on the expression of MMP-1, MMP-7, MMP-8, and MMP-13 in healthy liver tissue and fibrotic liver tissue using qRT-PCR.

Results: According to the WHO-IWGE classification, patients with functional cysts (CE1 and CE2) had the highest percentage (46.6%). MMP-1, MMP-7, MMP-8, and MMP-13 expression levels were significantly higher in fibrotic liver than in normal liver tissue. MMP-13 and MMP-1 had the highest and lowest expression levels among MMPs. Compared to the normal group, the fold change for MMP-13 in the fibrotic group was greater than 12 and had the highest AUC value (AUC= 0.8283).

Conclusion: Our findings suggest that E. granulosus-derived products might be involved in regulating host MMPs. Thus, MMPs may be considered potential biomarkers for predicting CE prognosis. Because of the non-normal distribution of our patients’ CE types, further research, particularly on circulation MMPs, is needed to confirm the potential role of MMPs in CE pathogenesis and to follow up on CE patients.

[1]
Bosco A, Alves LC, Cociancic P, Amadesi A, Pepe P, Morgoglione ME. Epidemiology and spatial distribution of Echinococcus granulosus in sheep and goats slaughtered in a hyperendemic European Mediterranean area. Parasites Vectors 2021; 141: 421.
[2]
Budke CM, Casulli A, Kern P, Vuitton DA. Cystic and alveolar echinococcosis: Successes and continuing challenges. PLoS neglected tropical disease 2017; 4: e0005477.
[3]
da Silva AM. Human echinococcosis: A neglected disease. Gastroenterol Res Pract 2010; 2010: 1-9.
[http://dx.doi.org/10.1155/2010/583297] [PMID: 20862339]
[4]
International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop 2003; 85(2): 253-61.
[http://dx.doi.org/10.1016/S0001-706X(02)00223-1] [PMID: 12606104]
[5]
Zhang W, Li J, McManus DP. Concepts in immunology and diagnosis of hydatid disease. Clin Microbiol Rev 2003; 16(1): 18-36.
[http://dx.doi.org/10.1128/CMR.16.1.18-36.2003] [PMID: 12525423]
[6]
Niu F, Chong S, Qin M, Li S, Wei R, Zhao Y. Mechanism of fibrosis induced by Echinococcus spp. Diseases 2019; 7(3): 51.
[http://dx.doi.org/10.3390/diseases7030051]
[7]
Wang J, Zhang C, Wei X, Blagosklonov O, Lv G, Lu X. TGF-β and TGF-β/Smad signaling in the interactions between Echino-coccus multilocularis and its hosts. PloS one 2013; e55379.
[8]
Zhang C, Wang L, Ali T, et al. Hydatid cyst fluid promotes peri-cystic fibrosis in cystic echinococcosis by suppressing miR-19 expression. Parasit Vectors 2016; 9(1): 278.
[http://dx.doi.org/10.1186/s13071-016-1562-x] [PMID: 27177776]
[9]
Xu F, Liu C, Zhou D, Zhang L. TGF-β/SMAD pathway and its regulation in hepatic fibrosis. J Histochem Cytochem 2016; 64(3): 157-67.
[http://dx.doi.org/10.1369/0022155415627681] [PMID: 26747705]
[10]
Yan C, Wang L, Li B, Zhang B-B, Zhang B, Wang Y-H. The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis. Parasit Vectors 2015; 4; 8: 70.
[11]
Cui N, Hu M, Khalil RA. Biochemical and biological attributes of matrix metalloproteinases. Prog Mol Biol Transl Sci 2017; 147: 1-73.
[http://dx.doi.org/10.1016/bs.pmbts.2017.02.005] [PMID: 28413025]
[12]
Serra R. Matrix metalloproteinases in health and disease. Biomolecules 2020; 10(8): 1138.
[http://dx.doi.org/10.3390/biom10081138] [PMID: 32752285]
[13]
Mansoor N, Wahid F, Azam M, et al. Molecular Mechanisms of complement system proteins and matrix metalloproteinases in the pathogenesis of age-related macular degeneration. Curr Mol Med 2019; 19(10): 705-18.
[http://dx.doi.org/10.2174/1566524019666190828150625] [PMID: 31456517]
[14]
Naim A, Pan Q, Baig MS. Matrix metalloproteinases (MMPs) in liver diseases. J Clin Exp Hepatol 2017; 7(4): 367-72.
[http://dx.doi.org/10.1016/j.jceh.2017.09.004] [PMID: 29234202]
[15]
Badra G, Lotfy M, El-Refaie A, et al. Significance of serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in chronic hepatitis C patients. Acta Microbiol Immunol Hung 2010; 57(1): 29-42.
[http://dx.doi.org/10.1556/AMicr.57.2010.1.3] [PMID: 20350877]
[16]
Duarte S, Baber J, Fujii T, Coito AJ. Matrix metalloproteinases in liver injury, repair and fibrosis. Matrix Biol 2015; 44-46: 147-56.
[http://dx.doi.org/10.1016/j.matbio.2015.01.004]
[17]
Mirzavand S, Rafiei A, Teimoori A, et al. Gene expression in human liver fibrosis associated with Echinococcus granulosus sen-su lato. Parasitol Res 2020; 119(7): 2177-87.
[http://dx.doi.org/10.1007/s00436-020-06700-9] [PMID: 32377911]
[18]
Singh KP, Gerard HC, Hudson AP, Boros DL. Dynamics of collagen, MMP and TIMP gene expression during the granuloma-tous, fibrotic process induced by Schistosoma mansoni eggs. Ann Trop Med Parasitol 2004; 98(6): 581-93.
[http://dx.doi.org/10.1179/000349804225021316] [PMID: 15324465]
[19]
Hemmann S, Graf J, Roderfeld M, Roeb E. Expression of MMPs and TIMPs in liver fibrosis – a systematic review with special emphasis on anti-fibrotic strategies. J Hepatol 2007; 46(5): 955-75.
[http://dx.doi.org/10.1016/j.jhep.2007.02.003] [PMID: 17383048]
[20]
Weiskirchen R, Weiskirchen S, Tacke F. Recent advances in understanding liver fibrosis: bridging basic science and individ-ualized treatment concepts. F1000 Res 2018; 7: 921.
[http://dx.doi.org/10.12688/f1000research.14841.1] [PMID: 30002817]
[21]
George J, Tsutsumi M, Tsuchishima M. MMP-13 deletion decreases profibrogenic molecules and attenuates N -nitrosodimethylamine-induced liver injury and fibrosis in mice. J Cell Mol Med 2017; 21(12): 3821-35.
[http://dx.doi.org/10.1111/jcmm.13304] [PMID: 28782260]
[22]
Geervliet E, Bansal R. Matrix metalloproteinases as potential biomarkers and therapeutic targets in liver diseases. Cells 2020.
[http://dx.doi.org/10.3390/cells9051212]
[23]
Endo H, Niioka M, Sugioka Y, et al. Matrix metalloproteinase-13 promotes recovery from experimental liver cirrhosis in rats. Pathobiology 2011; 78(5): 239-52.
[http://dx.doi.org/10.1159/000328841] [PMID: 21849805]
[24]
Akhtar N, Rasheed Z, Ramamurthy S, Anbazhagan AN, Voss FR, Haqqi TM. MicroRNA-27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytes. Arthritis Rheum 2010; 62(5): 1361-71.
[http://dx.doi.org/10.1002/art.27329] [PMID: 20131257]
[25]
Jin X, Guo X, Zhu D, Ayaz M, Zheng Y. miRNA profiling in the mice in response to Echinococcus multilocularis infection. Acta Trop 2017; 166: 39-44.
[http://dx.doi.org/10.1016/j.actatropica.2016.10.024] [PMID: 27810427]
[26]
Harty MW, Huddleston HM, Papa EF, et al. Repair after cholestatic liver injury correlates with neutrophil infiltration and matrix metalloproteinase 8 activity. Surgery 2005; 138(2): 313-20.
[http://dx.doi.org/10.1016/j.surg.2005.04.009] [PMID: 16153442]
[27]
Giannandrea M, Parks WC. Diverse functions of matrix metalloproteinases during fibrosis. Dis Model Mech 2014; 7(2): 193-203.
[http://dx.doi.org/10.1242/dmm.012062] [PMID: 24713275]
[28]
Li Z, Zhang C, Li L, Bi X, Li L, Yang S. The local immune response during Echinococcus granulosus growth in a quantitative hepatic experimental model. Sci Rep 2019; 9(1): 19612.
[29]
Hasanzadeh A, Rafiei A, Kazemi M, Beiromvand M, Bahreini A, Khanahmad H. The role of tissue inhibitor of metalloproteinase-1 and 2 in Echinococcus granulosus senso lato-induced human hepatic fibrosis. Acta Parasitol 2022; 67(2): 851-7.
[30]
Prato M, D’Alessandro S, Van den Steen PE, et al. Natural haemozoin modulates matrix metalloproteinases and induces mor-phological changes in human microvascular endothelium. Cell Microbiol 2011; 13(8): 1275-85.
[http://dx.doi.org/10.1111/j.1462-5822.2011.01620.x] [PMID: 21707906]
[31]
He X, Wang Y, Fan X, et al. A schistosome miRNA promotes host hepatic fibrosis by targeting transforming growth factor beta receptor III. J Hepatol 2020; 72(3): 519-27.
[http://dx.doi.org/10.1016/j.jhep.2019.10.029] [PMID: 31738999]
[32]
Alizadeh Z, Mahami-Oskouei M, Spotin A, et al. Parasite-derived microRNAs in plasma as novel promising biomarkers for the early detection of hydatid cyst infection and post-surgery follow-up. Acta Trop 2020; 202: 105255.
[http://dx.doi.org/10.1016/j.actatropica.2019.105255] [PMID: 31682814]
[33]
Örsten S, Baysal İ, Yabanoglu-Ciftci S, et al. Can parasite-derived microRNAs differentiate active and inactive cystic echino-coccosis patients? Parasitol Res 2022; 121(1): 191-6.
[http://dx.doi.org/10.1007/s00436-021-07382-7] [PMID: 34811587]
[34]
Huang CC, Chuang JH, Chou MH, et al. Matrilysin (MMP-7) is a major matrix metalloproteinase upregulated in biliary atresia-associated liver fibrosis. Mod Pathol 2005; 18(7): 941-50.
[http://dx.doi.org/10.1038/modpathol.3800374] [PMID: 15696117]