TGF-β signaling in the kidney: profibrotic and protective effects

Abstract

Transforming growth factor-β (TGF-β) is generally considered as a central mediator of fibrotic diseases. Indeed, much focus has been placed on inhibiting TGF-β and its downstream targets as ideal therapeutic strategies. However, pharmacological blockade of TGF-β has not yet translated into successful therapy for humans, which may be due to pleiotropic effects of TGF-β signaling. Equally, TGF-β signaling as a protective response in kidney injury has been relatively underexplored. An emerging body of evidence from experimental kidney disease models indicates multifunctionality of TGF-β capable of inducing profibrotic and protective effects. This review discusses recent advances highlighting the diverse roles of TGF-β in promoting not only renal fibrosis but also protective responses of TGF-β signaling. We review, in particular, growing evidence that supports protective effects of TGF-β by mechanisms which include inhibiting inflammation and induction of autophagy. Additional detailed studies are required to fully understand the diverse mechanisms of TGF-β actions in renal fibrosis and inflammation that will likely direct toward effective antifibrotic therapies.

PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury

“…Briefly, smad3 has been proven to play a pivotal pathogenic role; while smad7, as an inhibitory member of the smad superfamily, antagonizes the action of smad33435. Numerous known factors related to tissue repair and tissue homeostasis are regulated in a TGF-β/smad-dependent manner3637. Based on the abovementioned knowledge, therapeutic approaches that involve blocking the pathogenic action of TGF-β on multiple levels have been developed to control the progression of renal fibrosis.…”

Transplantation of Telocytes Attenuates Unilateral Ureter Obstruction-Induced Renal Fibrosis in Rats

“…Once combined with Smad4, the Smad complex is formed. The complex is then transferred to the nucleus to regulate target gene transcription, including Snail and ZEB1, and thus resulting in renal fibrosis [4, 40, 41]. In the present study, we detected significantly increased phosphorylation of Smad2 and Smad3 and the expression of Snail and ZEB1 in the UUO group; while telocyte treatment was able to decrease the phosphorylation and expression of these proteins, fibroblast treatment did not result in a significant change.…”

Dapagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, slows the progression of renal complications through the suppression of renal inflammation, endoplasmic reticulum stress and apoptosis in prediabetic rats

“…In addition, lipids or their breakdown products in non‐adipose tissue, also produce the key profibrotic factor, transforming growth factor‐β1 (TGF‐β1), which causes a fibrotic response, subsequently leading to organ dysfunction . Moreover, data from animals with metabolic syndrome have shown a correlation between hyperinsulinaemia and progressive tubulointersitial fibrosis, involving proliferation of the extracellular matrix and collagen deposition, which are the characteristics of renal injury in diabetes . Thus, the control of inflammation has great therapeutic potential with regard to the inhibition of progressive renal fibrosis.…”