Okada Hirokazu, Kalluri Raghu
Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Curr Mol Med. 2005 Aug;5(5):467-74. doi: 10.2174/1566524054553478.
Renal fibrosis is a common consequence and often a central feature of all the progressive renal diseases that lead to end-stage renal failure. In comparison to wound healing, during kidney fibrosis the length of the post-inflammatory phase often exceeds and continues unchecked resulting in scar formation. Infiltrating immune cells and a heterogeneous colony of interstitial cells derived from a variety of cellular origins such as resident mesenchymal cells, tubular epithelial cells, circulating fibrocytes, and bone marrow derived stem cells, communicate with each other and with inflamed and surviving parenchymal cells via a network of cytokines and adhesion molecules to populate the renal tubulointerstitial space during early fibrogenesis. Such fibroblasts subsequently secrete abundant extracellular matrix to achieve architectural remodeling in parallel with functional deterioration. Renal fibrosis is a dominant determinant of the clinical outcome of patients and yet for the most part, current therapies are ineffective or only marginally effective. This review highlights recent advances in our understanding of the cellular and molecular events leading to the progression of renal fibrosis.
肾纤维化是所有导致终末期肾衰竭的进行性肾脏疾病的常见后果，且往往是其核心特征。与伤口愈合相比，在肾纤维化过程中，炎症后阶段的时长常常超过正常范围且不受控制地持续下去，从而导致瘢痕形成。浸润的免疫细胞以及源自多种细胞来源（如驻留间充质细胞、肾小管上皮细胞、循环纤维细胞和骨髓来源的干细胞）的异质性间质细胞群体，通过细胞因子和黏附分子网络相互交流，并与炎症状态下及存活的实质细胞进行交流，从而在早期纤维化形成过程中填充肾小管间质空间。这些成纤维细胞随后分泌大量细胞外基质，以实现结构重塑，同时伴有功能恶化。肾纤维化是患者临床预后的主要决定因素，但在很大程度上，目前的治疗方法无效或仅具有微弱疗效。本综述重点介绍了我们对导致肾纤维化进展的细胞和分子事件的最新认识进展。
