肾脏周细胞-肌成纤维细胞转分化的病理机制及中药的干预作用

Pathomechanisms of pericyte-myofibroblast transition in kidney and interventional effects of Chinese herbal medicine

在肾脏,周细胞(pericyte)是肾间质中肌成纤维细胞(myofibroblast,MyoF)的主要来源。周细胞-肌成纤维细胞转分化(pericyte-myofibroblast transition,PMT)是肾间质纤维化(renal interstitial fibrosis,RIF)重要病理机制之一,其中,周细胞的募集、活化与分离以及周细胞源性促红细胞生成素缺乏是促进RIF形成的主要原因。在PMT启动过程中,周细胞的活化及其与微血管的分离受控于多条信号转导途径,这些信号通路包括转化生长因子-β(transforming growth factor β,TGF-β)通路、血管内皮生长因子受体(vascular endothelial growth factor receptor,VEGFR)通路、血小板源性生长因子受体(platelet derived growth factor receptor,PDGFR)通路;阻断这些信号通路不仅能抑制PMT,而且,能遏制肾脏毛细血管减少,改善RIF。临床上,很多中药复方、单味中药及其提取物等都具有改善RIF的明确疗效,其中,一些中药的干预作用可能与周细胞及其PMT相关。基于此,"PMT及其药物干预的研究"将会成为中药抗脏器纤维化研究领域的重要发展方向。

In the kidney, pericyte is the major source of myofibroblast(MyoF) in renal interstitium. It is reported that pericyte-myofibroblast transition(PMT)is one of the important pathomechanisms of renal interstitial fibrosis(RIF). Among them, the main reasons for promoting RIF formation include pericyte recruitment, activation and isolation, as well as the lack of pericyte-derived erythropoietin. During the PMT startup process, pericyte activation and its separation from microvessels are controlled by multiple signal transduction pathways, such as transforming growth factor-β(TGF-β)pathway, vascular endothelial growth factor receptor(VEGFR) pathway and platelet derived growth factor receptor(PDGFR) pathway;Blocking of these signaling pathways can not only inhibit PMT, but also suppress renal capillaries reduction and further alleviate RIF. In clinic, many traditional Chinese medicine compound prescriptions, single traditional Chinese herbal medicine(CHM) and their extracts have the clear effects in alleviating RIF, and some of their intervention actions may be related to pericyte and its PMT. Therefore, the studies on PMT and its drug intervention will become the main development direction in the research field of anti-organ fibrosis by CHM.