title: Zinc transporter 7 induced by high glucose attenuates epithelial-to-mesenchymal transition of peritoneal mesothelial cells.
abstract: Zinc (Zn) is an essential micronutrient and cytoprotectant involved in preventing many types of epithelial-to-mesenchymal transition (EMT)-driven fibrosis in vivo. The zinc-transporter family SLC30A (ZnT) is a pivotal factor in the regulation of Zn homeostasis. However, its function in EMT in peritoneal mesothelial cells (PMCs) remains unknown. This study explored the regulation of zinc transporters and the role they play in cell EMT, particularly in rat peritoneal mesothelial cells (RPMCs), surrounding glucose concentrations and the molecular mechanism involved. The effects of high glucose (HG) on zinc transporter gene expression were measured in RPMCs by real-time PCR. We explored ZnT7 (Slc30A7): the effect of ZnT7 over-expression and siRNA-mediated knock-down on HG-induced EMT was investigated as well as the underlying molecular mechanisms. Over-expression of ZnT7 resulted in significantly inhibited HG-induced EMT in RPMCs, while inhibition of ZnT7 expression using a considerable siRNA-mediated knock-down of RPMCs increased the levels of EMT. Furthermore, over-expression of ZnT7 is accompanied by down-regulation of TGF-β/Smad pathway, phospho-Smad3,4 expression levels. The finding suggests that the zinc-transporting system in RPMCs is influenced by the exposure to HG. The ZnT7 may account for the inhibition of HG-induced EMT in RPMCs, likely through targeting TGF-β/Smad signaling.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, China Medical University, 155th Nanjing North Street, Shenyang, Liaoning, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Liang
authors.forename: Baolei
authors.initials: B
authors.lastname: Guo
authors.forename: Lixia
authors.initials: L
authors.lastname: Sun
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Chi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cai
authors.forename: Lining
authors.initials: L
authors.lastname: Wang
authors.forename: Jianfei
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D010537:Peritoneum / Q000166:cytology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; C000592025:Slc30A7 protein, rat; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D005947:Glucose