Rojas Andres, Chang Fan-Chi, Lin Shuei-Liong, Duffield Jeremy S
Renal Division & Center for Lung Biology, Department of Medicine, and Institute of Stem Cell & Regenerative Medicine, University of Washington, Seattle, WA, USA.
Clin Nephrol. 2012 May;77(5):400-8. doi: 10.5414/cn107371.
Fibrosis of the kidney is a disease affecting millions worldwide and is a harbinger of progressive loss of organ function resulting in organ failure. Recent findings suggest that understanding mechanisms of development and progression of fibrosis will lead to new therapies urgently required to counteract loss of organ function. Recently, little-known cells that line the kidney microvasculature, known as pericytes, were identified as the precursor cells which become the scar-forming myofibroblasts. Kidney pericytes are extensively branched cells located in the wall of capillaries, embedded within the microvascular basement membrane, and incompletely envelope endothelial cells with which they establish focal contacts. In response to kidney injuries, pericytes detach from endothelial cells and migrate into the interstitial space where they undergo a transition into myofibroblasts. Detachment leads to fibrosis but also leaves an unstable endothelium, prone to rarefaction. Endothelial-pericyte crosstalk at the vascular endothelial growth factor receptors and platelet derived growth factor receptors in response to injury have been identified as major new targets for therapeutic intervention.
肾纤维化是一种影响全球数百万人的疾病,是器官功能逐渐丧失直至器官衰竭的先兆。最近的研究结果表明,了解纤维化的发生和发展机制将带来对抗器官功能丧失急需的新疗法。最近,人们发现排列在肾脏微血管内的鲜为人知的细胞——周细胞,是形成瘢痕的肌成纤维细胞的前体细胞。肾周细胞是广泛分支的细胞,位于毛细血管壁内,嵌入微血管基底膜中,并与内皮细胞建立局灶性接触,不完全包裹内皮细胞。在肾脏损伤的反应中,周细胞从内皮细胞脱离并迁移到间质空间,在那里它们转变为肌成纤维细胞。脱离会导致纤维化,但也会使内皮不稳定,易于稀疏。损伤时血管内皮生长因子受体和血小板衍生生长因子受体处的内皮-周细胞相互作用已被确定为治疗干预的主要新靶点。