Extracellular matrix turnover: phytochemicals target and modulate the dual role of matrix metalloproteinases (MMPs) in liver fibrosis

Abstract Extracellular matrix (ECM) resolution by matrix metalloproteinases (MMPs) is a well‐documented mechanism. MMPs play a dual and complex role in modulating ECM degradation at different stages of liver fibrosis, depending on the timing and levels of their expression. Increased MMP‐1 combats disease progression by cleaving the fibrillar ECM. Activated hepatic stellate cells (HSCs) increase expression of MMP‐2, ‐9, and ‐13 in different chemicals‐induced animal models, which may alleviate or worsen disease progression based on animal models and the stage of liver fibrosis. In the early stage, elevated expression of certain MMPs may damage surrounding tissue and activate HSCs, promoting fibrosis progression. At the later stage, downregulation of MMPs can facilitate ECM accumulation and disease progression. A number of phytochemicals modulate MMP activity and ECM turnover, alleviating disease progression. However, the effects of phytochemicals on the expression of different MMPs are variable and may depend on the disease models and stage, and the dosage, timing and duration of phytochemicals used in each study. Here, we review the most recent advances in the role of MMPs in the effects of phytochemicals on liver fibrogenesis, which indicates that further studies are warranted to confirm and define the potential clinical efficacy of these phytochemicals.