Abstract
Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Transforming growth factor-β (TGF-β) has been long considered as a key mediator of renal fibrosis. In addition, TGF-β also acts as a potent anti-inflammatory cytokine that negatively regulates renal inflammation. Thus, blockade of TGF-β inhibits renal fibrosis while promoting inflammation, revealing a diverse role for TGF-β in CKD. It is now well documented that TGF-β1 activates its downstream signaling molecules such as Smad3 and Smad3-dependent non-coding RNAs to transcriptionally and differentially regulate renal inflammation and fibrosis, which is negatively regulated by Smad7. Therefore, treatments by rebalancing Smad3/Smad7 signaling or by specifically targeting Smad3-dependent non-coding RNAs that regulate renal fibrosis or inflammation could be a better therapeutic approach. In this review, the paradoxical functions and underlying mechanisms by which TGF-β1 regulates in renal inflammation and fibrosis are discussed and novel therapeutic strategies for kidney disease by targeting downstream TGF-β/Smad signaling and transcriptomes are highlighted.
Highlights
Increasing evidence shows that chronic kidney disease (CKD) is a global-burden-disease (Romagnani et al, 2017)
During the progression of CKD, renal function is impaired with a loss of nephrons and the development of renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM) components, reduction in glomerular filtration rate (GFR), and abnormal albuminuria (Glassock et al, 2017)
Smad4 may play a diverse role in renal fibrosis and inflammation and may not be a specific therapeutic target for CKD
Summary
Increasing evidence shows that chronic kidney disease (CKD) is a global-burden-disease (Romagnani et al, 2017). Conditional deletion of TβRII from mice results in protection against TGF-β/Smad3-mediated renal fibrosis while enhancing NF-κB-driven renal inflammation (Meng et al, 2012a). Smad4 may play a diverse role in renal fibrosis and inflammation and may not be a specific therapeutic target for CKD.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
