The Role of Tissue Inhibitor of Metalloproteinase-1 and 2 in Echinococcus granulosus senso lato-Induced Human Hepatic Fibrosis

Abstract

Introduction The main mechanism underlying hepatic fibrosis is the imbalance between tissue Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs). This study aimed to investigate the potential role of TIMP-1 and TIMP-2 in the process of hepatic fibrosis caused by Echinococcus granulosus senso lato (E. granulosus s.l.). Methods The expressions levels of TIMP-1 and TIMP-2 mRNAs were evaluated in fibrotic and normal hepatic tissues of 30 patients with Cystic Echinococcus (CE) using qRT-PCR. Moreover, their serum levels of TIMP-1 were assessed before CE cyst removal and 6 months after surgery using ELISA. Results The qRT-PCR results showed that the expression levels of TIMP-1 and TIMP-2 mRNAs were significantly higher in the fibrotic hepatic tissue compared to the normal liver tissue, in a way that the TIMP-1 and TIMP-2 mRNA expression levels were 19.07 and 6.58 folds higher in the fibrotic tissue compared to the normal liver tissue. Among these TIMPs, TIMP-1 exhibited the higher area under the curve (AUC) value for predicting liver fibrosis. However, we could not find a significant difference in the serum levels of TIMP-1 before and after the cyst removal procedure (p = 0.48). Conclusions For the first time, our study showed that the significant overexpression of both TIMP mRNAs in the fibrotic liver tissue of the CE patients may be due to the increased expression of MMPs in the peri-cystic tissue. However, we could not find a significant difference in the pre- and post-operative TIMP-1 levels, which may be due to recurrence or heterogeneity in the cyst type. Therefore, performing further studies with a larger sample size of the CE patients is recommended.