Department of Nephrology, RWTH University of Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
Pediatr Nephrol. 2012 Jul;27(7):1041-50. doi: 10.1007/s00467-011-1892-z. Epub 2011 May 21.
The platelet-derived growth factor (PDGF) family plays an important role in embryonic development, malignancy, wound healing, atherosclerosis, and fibrosis in multiple organs. It belongs to the best-characterized growth factor systems in normal and diseased kidneys, and there is accumulating evidence that members of the PDGF family are key players in the development of renal fibrosis independent of the underlying kidney disease. All components of the PDGF system, consisting of four isoforms (PDGF-A, -B, -C, -D) and two receptor chains (PDGFR-α and -β), are constitutively or inducibly expressed in most renal cells. They regulate multiple pathophysiologic events, ranging from cell proliferation and migration, extracellular matrix accumulation and production of pro- and anti-inflammatory mediators, to tissue permeability and hemodynamics. This review focuses on advances in defining the roles of different PDGF isoforms in the development of glomerulosclerosis and tubulointerstitial fibrosis. The recent identification of endogenous PDGF inhibitors offers additional novel therapeutic strategies.
血小板衍生生长因子 (PDGF) 家族在胚胎发育、恶性肿瘤、伤口愈合、动脉粥样硬化和多个器官的纤维化中发挥重要作用。它属于正常和患病肾脏中研究最充分的生长因子系统之一,越来越多的证据表明 PDGF 家族成员是独立于潜在肾脏疾病的肾脏纤维化发展的关键参与者。PDGF 系统的所有成分,包括四个同工型(PDGF-A、-B、-C 和 -D)和两个受体链(PDGFR-α 和 -β),在大多数肾脏细胞中持续或诱导表达。它们调节多种病理生理事件,包括细胞增殖和迁移、细胞外基质积累和产生促炎和抗炎介质,以及组织通透性和血液动力学。这篇综述重点介绍了不同 PDGF 同工型在肾小球硬化和肾小管间质纤维化发展中的作用的最新进展。最近发现的内源性 PDGF 抑制剂提供了额外的新治疗策略。