title: Oxymatrine Inhibits Renal Tubular EMT Induced by High Glucose via Upregulation of SnoN and Inhibition of TGF-β1/Smad Signaling Pathway.
abstract: Transforming growth factor-β1 (TGF-β1) signaling has been shown to play a critical role in the development of diabetic nephropathy (DN). The nuclear transcription co-repressor Ski-related novel protein N (SnoN) is an important negative regulator of TGF-β1/Smad signal transduction, and subsequent biological responses including tubule epithelial-mesenchymal transition (EMT), extracellular matrix accumulation and tubulointerstitial fibrosis. Oxymatrine (OM) is an alkaloid extracted from the Chinese herb Sophora japonica and has been demonstrated to prevent fibrosis. However, the anti-fibrosis effect of OM in DN is still unclear. In this study, we cultured normal rat renal tubular epithelial cells (NRK52Es) in high glucose and high glucose plus OM, and detected the expression of E-cadherin, α-SMA, FN, TGF-β1, SnoN, Arkadia, p-Smad2 and p-Smad3 and poly-ubiquitination of SnoN. The results showed that E-cadherin and SnoN expression in NRK52Es decreased significantly, but poly-ubiquitination of SnoN, TGF-β1, α-SMA, FN, Arkadia, p-Smad2 and p-Smad3 expression significantly increased due to high glucose stimulation, which could be almost completely reversed by OM, suggesting that OM may alleviate EMT induced by high glucose via upregulating SnoN expression and inhibiting TGF-β1/Smad signaling pathway activation. Hence, OM could be a novel therapeutic for DN.
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: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
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: 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: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D029909:Sophora / Q000737:chemistry; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D000093842:Matrines
chemical_list: D000470:Alkaloids; D005353:Fibronectins; D005947:Glucose; D009419:Nerve Tissue Proteins; D011807:Quinolizines; D051785:Smad Proteins; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D044767:Ubiquitin-Protein Ligases; C511209:Skil_v1 protein, rat; C037573:oxymatrine; D000093842:Matrines; C550853:Rnf111 protein, rat