title: Small interfering RNA targeting ILK inhibits EMT in human peritoneal mesothelial cells through phosphorylation of GSK‑3β.
abstract: Emerging evidence has suggested that human peritoneal mesothelial cells (HPMCs) undergo epithelial‑mesenchymal transition (EMT) in peritoneal fibrosis. The molecular mechanisms underlying peritoneal fibrosis and the key molecules involved are not yet fully elucidated. In order to enhance the understanding of peritoneal fibrosis, the present study investigated the roles of integrin‑linked kinase (ILK) and glycogen synthase kinase 3β (GSK‑3β) in high glucose‑induced phenotypic alterations of HPMCs. It was observed that HPMCs exhibited a cobblestone morphology under normal glucose conditions, whereas under high glucose conditions they had a spindle morphology. Additionally, under high glucose conditions it was found that E‑cadherin expression was decreased and vimentin expression was increased in HPMCs, suggesting HPMCs underwent EMT. ILK expression in high glucose conditions was also increased in a dose‑ and time‑dependent manner. The role of ILK in the induction of EMT in HPMCs was further investigated using small interfering RNA (siRNA). Following knockdown of ILK gene expression by siRNA, low vimentin expression as well as high E‑cadherin expression were observed, suggesting that EMT was inhibited. ILK‑knockdown also inhibited phosphorylation of GSK‑3β. These results indicate that ILK‑knockdown inhibits EMT of HPMCs through inhibition of GSK‑3β phosphorylation. These findings suggest that ILK may be used as a novel diagnostic and therapeutic target for HPMC fibrosis in the future.
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Lingrong
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Youming
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Fuyou
authors.initials: F
authors.lastname: Liu
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D010537:Peritoneum / Q000166:cytology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000099200:Scaffold Protein ILK
chemical_list: D015820:Cadherins; D005947:Glucose; D038362:Glycogen Synthase Kinase 3; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK