title: SnoN upregulation ameliorates renal fibrosis in diabetic nephropathy.
abstract: Progressive reduction of SnoN is associated with gradual elevation of TGF-β1 during diabetic nephropathy progression, suggesting SnoN to be a possible mediator of TGF-β1 signaling, with potential therapeutic benefits against TGF- β1 -induced renal fibrosis. To characterize SnoN for its role in renal fibrosis, we assessed SnoN expression patterns in response to high glucose stress, and evaluated the effects of upregulating SnoN on renal fibrosis. High glucose stress induced significantly elevated SnoN, TGF-β1, and Arkadia transcription; however, significantly reduced SnoN protein levels were observed under these conditions. Upregulating the SnoN protein was achieved by Arkadia knockdown, which resulted in inhibited high glucose-induced epithelial-mesenchymal transition (EMT) in renal tubular cells, the onset phase of renal fibrosis. Alternatively, EMT was suppressed by dominantly expressed exogenous SnoN without interfering with TGF-β1. Overall, renal SnoN upregulation ameliorates renal fibrosis by relieving high glucose-induced EMT; these findings support a translational approach targeting SnoN for the treatment of diabetic nephropathy.
authors.affiliation: Department of Clinical Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Lirong
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, People's Hospital of Guizhou Province, Guiyang, Guizhou, China.
authors.forename: Changzhi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Nanyang Central Hospital, Nanyang, Henan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Guo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015820:Cadherins; D009419:Nerve Tissue Proteins; C511209:Skil_v1 protein, rat; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C550853:Rnf111 protein, rat; D044767:Ubiquitin-Protein Ligases; D005947:Glucose