TGF-ß1 signaling in kidney disease: From Smads to long non-coding RNAs.

ABSTRACT

Transforming growth factor-ß1 (TGF-ß1) has an essential role in the development of kidney diseases. However, targeting TGF-ß1 is not a good strategy for fibrotic diseases due to its multifunctional characteristic in physiology. A precise therapeutic target maybe identified by further resolving the underlying TGF-ß1 driven mechanisms in renal inflammation and fibrosis. Smad signaling is uncovered as a key pathway of TGF-ß1-mediated renal injury, where Smad3 is hyper-activated but Smad7 is suppressed. Mechanistic studies revealed that TGF-ß1/Smad3 is capable of promoting renal inflammation and fibrosis via regulating non-coding RNAs. More importantly, involvement of disease- and tissue-specific TGF-ß1-dependent long non-coding RNAs (lncRNA) have been recently recognized in a number of kidney diseases. In this review, current understanding of TGF-ß1 driven lncRNAs in the pathogenesis of kidney injury, diabetic nephropathy and renal cell carcinoma will be intensively discussed.