title: Role of Smad signaling in kidney disease.
abstract: Smads are the key intermediates of canonical transforming growth factor-beta (TGF-β) signaling. These intermediates are divided into three distinct subgroups based on their role in TGF-β family signal transduction: Receptor-regulated Smads (R-Smads) 1, 2, 3, 5 and 8, common Smad4, and inhibitory Smads6 and 7. TGF-β signaling through Smad pathway involves phosphorylation, ubiquitination, sumoylation, acetylation, and protein-protein interactions with mitogen-activated protein kinases, PI3K-Akt/PKB, and Wnt/GSK-3. Several studies have suggested that upregulation or downregulation of TGF-β/Smad signaling pathways may be a pathogenic mechanism in the progression of chronic kidney disease. Smad2 and 3 are the two major downstream R-Smads in TGF-β-mediated renal fibrosis, while Smad7 also controls renal inflammation. In this review, we characterize the role of Smads in kidney disease, describe the molecular mechanisms, and discuss the potential of Smads as a therapeutic target in chronic kidney disease.
authors.affiliation: Department of Geriatrics & General Medicine, Second Hospital of Jilin University, Changchun, 130041, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Second Hospital of Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130041, China.|Department of Nephrology, Jilin Province People's Hospital, Changchun, 130021, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Second Hospital of Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130041, China. 304882606@qq.com.
authors.forename: Shengmao
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Urology, The 2nd Hospital of Changchun, Changchun, 130062, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Nephrology, Second Hospital of Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130041, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta
keywords: Kidney disease; Renal fibrosis; Renal inflammation; Smad; TGF-β