ECM1: a novel matricellular protein with promising antifibrotic potential

Abstract

Although numerous compounds that target individual or multiple cells or pathways have demonstrated antifibrotic potential, the reality is that only a small number of candidates have progressed successfully to the clinical trials phase. It seems plausible that the development of antifibrotic therapies focusing on the removal of fibrosis-causing agents and factors affecting hepatic stellate cell (HSC) activation might hold promise for reducing and preventing liver disease. Moreover, these therapies need to be safe with little or no hepatotoxicity and/or adverse effects. In liver homoeostasis, transforming growth factor-beta (TGF-β) is secreted in a biologically inactive, the so-called latent TGF-β form (LTGF-β) associated in a non-covalent complex with the extracellular matrix (ECM).1 In response to injury, local LTGF-β complexes are converted into active TGF-β. Activation of LTGF-β is mediated by several signals, including integrins, thrombospondin, proteases and reactive oxygen species.2 During liver fibrosis, TGF-β acts as a master profibrogenic cytokine in promoting activation and myofibroblastic differentiation of HSC, a central event in liver fibrogenesis and ECM production.3 Therefore, the regulation of locally activated TGF-β levels might be an excellent therapeutic target for liver fibrogenesis. ECM protein-1 (ECM1) was recently identified2 as a critical gatekeeper in the healthy liver, contributing to normal architecture and physiological homoeostasis of cell–cell communication by …