title: Transforming growth factor-β and Smads.
abstract: Diabetic nephropathy (DN) is a major diabetic complication. Transforming growth factor-β(TGF-β) is a key mediator in the development of diabetic complications. It is well known that TGF-β exerts its biological effects by activating downstream mediators, called Smad2and Smad3, which is negatively regulated by an inhibitory Smad7. Recent studies also demonstrated that under disease conditions Smads act as signal integrators and interact with other signaling pathways such as the MAPK and NF-κB pathways. In addition, Smad2and Smad3 can reciprocally regulate target genes of TGF-β signaling. Novel research into microRNA has revealed the complexity of TGF-β signaling during DN. It has been found that TGF-β and elevated glucose concentration can positively regulate miR-192 and miR-377, but negatively regulate miR-29a in a diabetic milieu. These microRNAs are found to contribute to DN. Although targeting TGF-β may exert adverse effects on immune system, therapeutic approach against TGF-β signaling during DN still draws much attention. Blocking TGF-β signaling by neutralizing antibody, anti-sense oligonucleotides, and soluble receptors have been tested, but effects are limited. Gene transfer of Smad7 into diseased kidneys demonstrates a prominent inhibition on renal fibrosis and amelioration of renal impairment. Alteration of TGF-β-regulated microRNA expression in diseased kidneys may provide an alternative therapeutic approach against DN. In conclusion, TGF-β/Smad signaling plays a critical role in DN. A better understanding of the role of TGF-β/Smad signaling in the development of DN should provide an effective therapeutic strategy to combat DN.
authors.forename: Hui Yao
authors.initials: HY
authors.lastname: Lan
authors.forename: Arthur C K
authors.initials: ACK
authors.lastname: Chung
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000209:etiology*; D006801:Humans; D015398:Signal Transduction; D051785:Smad Proteins / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta