PDF(Pubmed)
Abstract：
We propose that the key initiators of renal fibrosis are myofibroblasts which originate from four predominant sources-fibroblasts, pericytes, endothelial cells and macrophages. Increased accumulation of renal interstitial myofibroblasts correlates with an increase in collagen, fibrillar proteins, and fibrosis severity. The canonical TGF-β pathway, signaling via Smad proteins, is the central molecular hub that initiates these cellular transformations. However, directly targeting these classical pathway molecules has proven challenging due their integral roles in metabolic process, and/or non-sustainable effects involving compensatory cross-talk with TGF-β. This review explores recently discovered alternative molecular targets that drive transdifferentiation into myofibroblasts. Discovering targets outside of the classical TGF-β/Smad pathway is crucial for advancing antifibrotic therapies, and strategically targeting the development of myofibroblasts offers a promising approach to control excessive extracellular matrix deposition and impede fibrosis progression.
摘要：
我们建议肾纤维化的关键引发剂是肌成纤维细胞，它们来自四个主要来源-成纤维细胞。周细胞,内皮细胞和巨噬细胞。肾间质肌成纤维细胞的积累增加与胶原蛋白的增加相关，纤维状蛋白质，和纤维化严重程度。典型的TGF-β途径，信号通过Smad蛋白，是启动这些细胞转化的中心分子中心。然而,直接靶向这些经典途径分子已被证明具有挑战性，因为它们在代谢过程中的不可或缺的作用，和/或涉及与TGF-β的代偿性串扰的不可持续效应。这篇综述探讨了最近发现的驱动转分化为肌成纤维细胞的替代分子靶标。发现经典TGF-β/Smad途径之外的靶标对于推进抗纤维化治疗至关重要。战略性地靶向肌成纤维细胞的发展提供了一种有希望的方法来控制过度的细胞外基质沉积和阻止纤维化进展。
