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 …

中文翻译：

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ECM1：一种具有前景广阔的抗纤维化潜力的新型基质细胞蛋白


尽管许多靶向单个或多个细胞或通路的化合物已显示出抗纤维化的潜力，但现实情况是，只有少数候选化合物成功进入临床试验阶段。专注于去除引起纤维化的药物和影响肝星状细胞 （HSC） 活化的因素的抗纤维化疗法的开发似乎似乎很有道理，这可能为减少和预防肝病带来希望。此外，这些疗法需要是安全的，几乎没有肝毒性和/或不良反应。在肝脏匀态中，转化生长因子-β （TGF-β） 以生物无活性的即所谓的潜伏 TGF-β 形式 （LTGF-β） 分泌，与细胞外基质 （ECM） 在非共价复合物中相关。在损伤时，局部 LTGF-β 复合物转化为活性 TGF-β。LTGF-β 的激活由多种信号介导，包括整合素、血小板反应蛋白、蛋白酶和活性氧.2 在肝纤维化期间，TGF-β 作为主要促纤维化细胞因子促进 HSC 的激活和肌纤维母细胞分化，这是肝纤维化生成和 ECM 产生的核心事件.3 因此，局部激活的 TGF-β 水平的调节可能是肝纤维化的极好治疗靶点。ECM 蛋白 1 （ECM1） 最近被确定2为健康肝脏中的关键守门人，通过...