title: MicroRNA-328 inhibits renal tubular cell epithelial-to-mesenchymal transition by targeting the CD44 in pressure-induced renal fibrosis.
abstract: Epithelial-mesenchymal transition (EMT) occurs in stressed tubular epithelial cells, contributing to renal fibrosis. Initial mechanisms promoting EMT are unknown. Pressure force is an important mechanism contributing to the induction and progression of renal fibrogenesis in ureteric obstruction. In our study of cultured rat renal tubular cells (NRK-52E) under 60 mmHg of pressure, we found that the epithelial marker E-cadherin decreased and mesenchymal markers, e.g., α-smooth muscle actin, fibronectin and Snail, increased. Pressure also induced the expression of connective tissue growth factor and transforming growth factor-β. MicroRNA array assays showed that pressure reduced miR-328 at the initial stage of pressurization. We identified a potential target sequence of miR-328 in rat CD44 3'-untranslated regions. In contrast with the miR-328 expression, CD44 expression was up-regulated at the initial pressurization stage. We also found that miR-328 expression decreased and CD44 increased in ureteric obstruction kidneys in the animal study. CD44 siRNA transfection significantly increased E-cadherin expression and inhibited pressure-induced EMT. Both hyaluronan binding peptide pep-1 and osteopontin neutralizing antibody inhibited pressure-induced EMT. Our results suggest that miR-328-mediated CD44 transient upregulation is an important trigger of the pressure-induced EMT in renal fibrosis.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yen-Cheng
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuh-Mou
authors.initials: YM
authors.lastname: Sue
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chung-Te
authors.initials: CT
authors.lastname: Liu
authors.affiliation: Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors.forename: Yung-Ho
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tso-Hsiao
authors.initials: TH
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D015820:Cadherins / Q000235:genetics; D055513:Connective Tissue Growth Factor / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005353:Fibronectins / Q000235:genetics; D005355:Fibrosis / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000235:genetics*; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D053495:Osteopontin / Q000235:genetics; D011312:Pressure; D051381:Rats; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D014517:Ureteral Obstruction / Q000235:genetics
chemical_list: D000199:Actins; D015820:Cadherins; D005353:Fibronectins; D018960:Hyaluronan Receptors; D035683:MicroRNAs; C000604450:Snai2 protein, rat; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053495:Osteopontin; D055513:Connective Tissue Growth Factor