Regulation of Autophagy by TGF-β: Emerging Role in Kidney Fibrosis

Abstract

Autophagy is a highly conserved homoeostatic mechanism for cell survival under conditions of stress, and is widely implicated as an important pathway in many biological processes and diseases. In progressive kidney diseases, fibrosis represents the common pathway to end-stage kidney failure. Transforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine that has been established as a central mediator of kidney fibrosis. Recently emerging body of evidence from studies in renal cells in culture and experimental animal models suggests that TGF-β1 regulates autophagy and that autophagy regulates many critical aspects of normal and disease conditions associated with kidney fibrosis, such as tubulointerstitial fibrosis, glomerulosclerosis, and diabetic nephropathy. Here, we review the recent advances exploring the process of autophagy, its regulation by TGF-β1, and implication in the pathogenesis of progressive kidney fibrosis and injury responses. Understanding the cellular and molecular bases of this process is crucial for identifying potential new diagnostic and therapeutic targets of kidney fibrosis.

Transplanted Adipose Derived Mesenchymal Stem Cells Attenuate The Acute Renal Injury Induced by Cisplatin in Rats

“…Myofibroblast was the major source of extracellular matrix secretion. Renal tubular cells lost their epithelial phenotype and acquired new characteristic features of mesenchyme [11] .…”

Effect of Novel Gasotransmitter hydrogen sulfide on renal fibrosis and connexins expression in diabetic rats

“…It has been found that renal interstitial fibrosis is a concomitant pathological change in the occurrence and development of DN. 3 The disorder of matrix metalloproteinases and the tissue inhibitors of metalloproteinases (MMPS/TIMPs) have relation with nephropathy fibrosis. 4 Studies show that gap junction plays a significant role in ischemic renal injury and the occurrence and development of DN, and Cx43, Cx40 and Cx45 are the main connexins expressed in the kidney.…”

Autophagy in renal diseases

“…Potent sources of this protein are either macrophages or injured tubular epithelium. Via downstream signalling pathways, TGF-β1 induces type I collagen and fibronectin production in interstitial fibroblasts [51]. The balance between synthesis and degradation of collagen is crucial for the maintenance of tissue homeostasis.…”

“…In response to injury, they proliferate and produce excessive extracellular matrix. It has been shown that TGF-β1 induces autophagy in mesangial cells, thereby negatively regulating matrix production by the degradation of intracellular type I collagen [51]. Thus, TGF-β1 functions both as an inducer of collagen synthesis and as an inducer of autophagy and subsequent collagen degradation.…”

“…Thus, TGF-β1 functions both as an inducer of collagen synthesis and as an inducer of autophagy and subsequent collagen degradation. Even more intriguingly, TGF-β can also activate the mTOR pathway via PI3K/Akt, and therefore may exert both stimulatory and inhibitory effects on autophagy, probably depending on the specific cell type and context [51]. From in vivo studies [51], it seems that both upregulation and downregulation of autophagy may be involved in fibrogenesis.…”