title: 1,25(OH)2D3/VDR attenuates high glucose‑induced epithelial‑mesenchymal transition in human peritoneal mesothelial cells via the TGFβ/Smad3 pathway.
abstract: Epithelial-mesenchymal transition (EMT) has been recognized to accelerate peritoneal membrane dysfunction. 1,25(OH)2D3/vitamin D receptor (VDR) is important for preventing various types of EMT in vivo. However, its function on EMT and inflammation of human peritoneal mesothelial cells (HPMCs) remains to be elucidated. Therefore, the present study investigated the effects of 1,25(OH)2D3/VDR on high glucose (HG)‑induced EMT and inflammation in HPMCs and the underlying molecular mechanism. It was determined that HG reduced VDR expression, increased inflammatory cytokine expression, including transforming growth factor β (TGFβ) and interleukin‑6 (IL‑6) and phosphorylated‑SMAD family member 3 (p‑Smad3) expression. EMT was promoted as the expression level of the epithelial marker E‑cadherin was reduced, whereas expression levels of the mesenchymal markers α‑SMA and FN were increased. 1,25(OH)2D3 pretreatment inhibited the expression of inflammatory cytokines in HPMCs and attenuated HG‑induced EMT, possibly through inhibition of the TGFβ/Smad pathway by binding to its receptor VDR.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Benxi Center Hospital, China Medical University, Benxi, Liaoning 117000, P.R. China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Ma
mesh_terms: D002117:Calcitriol / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D058750:Epithelial-Mesenchymal Transition; D005947:Glucose / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D010537:Peritoneum / Q000166:cytology / Q000276:immunology; D018167:Receptors, Calcitriol / Q000276:immunology*; D015398:Signal Transduction; D051900:Smad3 Protein / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D016207:Cytokines; D018167:Receptors, Calcitriol; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D002117:Calcitriol; D005947:Glucose