Expression of MMPs and TIMPs in liver fibrosis – a systematic review with special emphasis on anti-fibrotic strategies

MiR-29a Assists in Preventing the Activation of Human Stellate Cells and Promotes Recovery From Liver Fibrosis in Mice

“…Interleukin 1 beta regulates inflammation signal pathway 28 and accelerates the expression level of MMP and TIMP. 29 It was reported that N-myc downstream regulated 1 regulates angiogenesis in hepatocellular carcinoma, 30 and B-cell leukemia/lymphoma 2 protein promotes apoptosis. MiR-29a indirectly regulated these fibrosis-related genes resulting in the suppression of liver fibrosis in this study.…”

“…In damaged liver, interleukin 1 beta can promote the expression of MMPs. In addition, the expression of TIMPs is also upregulated to inhibit MMP activity and lead to ECM accumulation 29 (Figure 1e,k and Figure 8b). It was reported that MMP2 expression increased and remained elevated during ECM accumulation, however the upregulated TIMP2 expression decreased after ceasing fibrosis induction in CCl 4 model mice.…”

An orally available small imidazolium salt ameliorates inflammation and fibrosis in a murine model of cholestasis

“…However, in the chronic liver injury, an increase in the expression of TIMP-1 partly contributed to the decreased turnover of ECM. 7,9 Therefore, strategies for blocking TIMP-1 had been explored to improve fibrosis. For example, antibody against TIMP-1 has been demonstrated to attenuate liver fibrosis in a CCl4 rat model, 23 while others reported that an increased expression of MMPs led to fibrolysis in animal models.…”

“…7 Based on such an analysis, therapeutic strategy aimed at restoring appropriate ECM compositions by regulating MMPs and TIMPs has also been attempted to attenuate and to resolve fibrosis. 8,9 Despite our extensive knowledge on the importance of inflammation and ECM remodeling in fibrogenesis and resolution, no effective drug therapy has been reported by simultaneously targeting these two key aspects with small molecules. In a recent study, 10 we have identified several imidazolium salts (IMSs) that can reduce collagen production in a cell-based screening, and further shown that one of the IMSs, 1,3-bisbenzylimidazolium bromide (DBZIM), can reduce the collagen content in the liver of a mouse cholestasis model.…”

Cellular and Molecular Mechanisms of Chronic Inflammation-Associated Organ Fibrosis

“…While the degradation of pathological fibrillar collagen by MMPs is a key event in the resolution of fibrosis, the degradation of normal ECM components in the early stages of fibrosis promotes deposition of newly synthesized collagen (Hemmann et al, 2007).…”