title: Parathyroid hormone induces epithelial-to-mesenchymal transition via the Wnt/β-catenin signaling pathway in human renal proximal tubular cells.
abstract: Epithelial-to-mesenchymal transition (EMT) has been shown to play an important role in renal fibrogenesis. Recent studies suggested parathyroid hormone (PTH) could accelerate EMT and subsequent organ fibrosis. However, the precise molecular mechanisms underlying PTH-induced EMT remain unknown. The present study was to investigate whether Wnt/β-catenin signaling pathway is involved in PTH-induced EMT in human renal proximal tubular cells (HK-2 cells) and to determine the profile of gene expression associated with PTH-induced EMT. PTH could induce morphological changes and gene expression characteristic of EMT in cultured HK-2 cells. Suppressing β-catenin expression or DKK1 limited gene expression characteristic of PTH-induced EMT. Based on the PCR array analysis, PTH treatment resulted in the up-regulation of 18 genes and down-regulation of 9 genes compared with the control. The results were further supported by a western blot analysis, which showed the increased Wnt4 protein expression. Wnt4 overexpression also promotes PTH-induced EMT in HK-2 cells. The findings demonstrated that PTH-induced EMT in HK-2 cells is mediated by Wnt/β-catenin signal pathway, and Wnt4 might be a key gene during PTH-induced EMT.
authors.affiliation: Department of Nephrology, General Hospital of Ji'nan Military Command Ji'nan 250031, China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Nephrology, General Hospital of Ji'nan Military Command Ji'nan 250031, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Nephrology, General Hospital of Ji'nan Military Command Ji'nan 250031, China.
authors.forename: Raohai
authors.initials: R
authors.lastname: Ding
authors.affiliation: Department of Nephrology, General Hospital of Ji'nan Military Command Ji'nan 250031, China.
authors.forename: Hongdong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Nephrology, General Hospital of Ji'nan Military Command Ji'nan 250031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Shanghai Jiaotong University Affiliated First People's Hospital 85 Wu Jin Road, Shanghai 200080, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Nephrology, General Hospital of Ji'nan Military Command Ji'nan 250031, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D060528:Wnt4 Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D010281:Parathyroid Hormone; C555581:WNT4 protein, human; D060528:Wnt4 Protein; D051176:beta Catenin
keywords: Epithelial-to-mesenchymal transition; Wnt/β-catenin signal pathway; parathyroid hormone; renal tubular epithelial cell