TGF-β: the connecting link between nephropathy and fibrosis

Abstract

Renal fibrosis is the usual outcome of an excessive accumulation of extracellular matrix (ECM) that frequently occurs in membranous and diabetic nephropathy. The result of renal fibrosis would be end-stage renal failure, which requires costly dialysis or kidney transplantation. Renal fibrosis typically results from chronic inflammation via production of several molecules, such as growth factors, angiogenic factors, fibrogenic cytokines, and proteinase. All of these factors can stimulate excessive accumulation of ECM components through epithelial to mesenchymal transition (EMT), which results in renal fibrosis. Among these, transforming growth factor-beta (TGF-β) is proposed to be the major regulator in inducing EMT. Besides ECM protein synthesis, TGF-β is involved in hypertrophy, proliferation, and apoptosis in renal cells. In particular, TGF-β is likely to be most potent and ubiquitous profibrotic factor acting through several intracellular signaling pathways including protein kinases and transcription factors. Factors that regulate TGF-β expression in renal cell include hyperglycemia, angiotensin II, advance glycation end products, complement activation (C5b-9), and oxidative stress. Over the past several years, the common understanding of the pathogenic factors that lead to renal fibrosis in nephropathy has improved considerably. This review will discuss the recent findings on the mechanisms and role of TGF-β in membranous and diabetic nephropathy.

An update on diabetic kidney disease, oxidative stress and antioxidant agents

“…Based on evidence, individuals with diabetic kidney disease often have deficiency in CoQ10 plasma levels compared to normal healthy subjects. Because of its antioxidant property, it is accepted that CoQ10 deficiency may impair the body’s defensive mechanisms against oxidative stress induced by hyperglycemia (24). Therefore, it is recommended that CoQ10 plays an important role in the pathogenesis of type 2 diabetic mellitus.…”

Role of the Wnt/β-catenin signaling pathway in inducing apoptosis and renal fibrosis in 5/6-nephrectomized rats

“…Dysregulation of this important signaling pathway is closely associated with the progression of renal fibrosis (3). Transforming growth factor (TGF)-β is typically regarded as the most potent profibrogenic cytokine and a central mediator of renal fibrosis (4). TGF-β is a primary ECM regulator, acting as an inducer of ECM synthesis and an inhibitor of ECM degradation, via the direct suppression of matrix metalloproteinases and induction of tissue inhibitors of metalloproteinases (5).…”

Role and Association of Inflammatory and Apoptotic Caspases in Renal Tubulointerstitial Fibrosis

“…Renal interstitial fibrosis typically resulted from chronic inflammation through production of related molecules, such as angiogenic factors, growth factors, fibrogenic cytokines and proteinase [30]. Renal inflammation is a universal response to infectious and noninfectious triggers.…”