title: TGF-β/Smad signaling in kidney disease.
abstract: Chronic progressive kidney diseases typically are characterized by active renal fibrosis and inflammation. Transforming growth factor-β1 (TGF-β1) is a key mediator in the development of renal fibrosis and inflammation. TGF-β1 exerts its biological effects by activating Smad2 and Smad3, which is regulated negatively by an inhibitory Smad7. In the context of fibrosis, although Smad3 is pathogenic, Smad2 and Smad7 are protective. Under disease conditions, Smads also interact with other signaling pathways, such as the mitogen-activated protein kinase and nuclear factor-κB pathways. In contrast to the pathogenic role of active TGF-β1, latent TGF-β1 plays a protective role in renal fibrosis and inflammation. Furthermore, recent studies have shown that TGF-β/Smad signaling plays a regulating role in microRNA-mediated renal injury. Thus, targeting TGF-β signaling by gene transfer of either Smad7 or microRNAs into diseased kidneys has been shown to retard progressive renal injury in a number of experimental models. In conclusion, TGF-β/Smad signaling plays a critical role in renal fibrosis and inflammation. Advances in understanding of the mechanisms of TGF-β/Smad signaling in renal fibrosis and inflammation during chronic kidney diseases should provide a better therapeutic strategy to combat kidney diseases.
authors: Li Ka Shing Institute of Health Sciences, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China. hylan@cuhk.edu.hk
authors: Hui Y
authors: HY
authors: Lan
authors: Arthur C-K
authors: AC
authors: Chung
mesh_terms: D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D020928:Mitogen-Activated Protein Kinases