Border W A, Noble N A
Division of Nephrology, University of Utah School of Medicine, Salt Lake City.
Am J Kidney Dis. 1993 Jul;22(1):105-13. doi: 10.1016/s0272-6386(12)70175-0.
Cytokines such as transforming growth factor-beta (TGF-beta) are peptide factors that regulate embryogenesis, development, inflammation, tissue repair, and carcinogenesis. Growing evidence indicates that dysregulation of cytokine actions may underlie the pathogenesis of serious autoimmune, degenerative, and fibrotic diseases. Studies in a model of acute mesangial proliferative glomerulonephritis show that overproduction of TGF-beta is the cause of pathologic accumulation of extracellular matrix in the nephritic glomeruli. Transforming growth factor-beta acts to increase matrix production, inhibit matrix degradation, and modulate matrix receptors in the glomerulonephritic rats. It may also play a role in the glomerular matrix build-up that is a central feature of diabetic nephropathy. Elevated expression of TGF-beta mRNA and TGF-beta protein were found in the glomeruli of diabetic rats along with increased levels of proteoglycans and other matrix components that are known to be induced by TGF-beta. The study of human diabetic glomeruli has also showed markedly elevated levels of TGF-beta protein. Glomeruli from normal kidneys and nonprogressive kidney disorders were negative. The striking ability of TGF-beta to cause exuberant matrix formation may be due to the fact that TGF-beta can induce its own production by resident cells at a site of injury. Thus, the potential for TGF-beta to do harm may be due to this autoinduction mechanism whereby TGF-beta expression can become chronic, creating a vicious circle. As the role that TGF-beta plays in chronic fibrotic diseases becomes better understood, it is likely that TGF-beta inhibitors will become important future drugs for treating these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
细胞因子如转化生长因子-β（TGF-β）是调节胚胎发生、发育、炎症、组织修复和致癌作用的肽类因子。越来越多的证据表明，细胞因子作用失调可能是严重自身免疫性、退行性和纤维化疾病发病机制的基础。在急性系膜增生性肾小球肾炎模型中的研究表明，TGF-β的过度产生是肾炎性肾小球中细胞外基质病理性积聚的原因。转化生长因子-β在肾小球肾炎大鼠中可增加基质产生、抑制基质降解并调节基质受体。它也可能在糖尿病肾病的主要特征——肾小球基质积聚中起作用。在糖尿病大鼠的肾小球中发现TGF-β mRNA和TGF-β蛋白表达升高，同时蛋白聚糖和其他已知由TGF-β诱导的基质成分水平也增加。对人类糖尿病肾小球的研究也显示TGF-β蛋白水平明显升高。来自正常肾脏和非进行性肾脏疾病的肾小球呈阴性。TGF-β导致大量基质形成的显著能力可能是由于TGF-β可诱导损伤部位的驻留细胞产生自身。因此，TGF-β造成损害的可能性可能归因于这种自身诱导机制，即TGF-β表达可能会变为慢性，从而形成恶性循环。随着对TGF-β在慢性纤维化疾病中作用的更好理解，TGF-β抑制剂很可能会成为未来治疗这些疾病的重要药物。（摘要截短至250字）
