title: [Effect of JAK/STAT pathway activation on high glucose-induced transdifferentiation in renal proximal tubular epithelial cells].
abstract: OBJECTIVE
  To evaluate the effect of JAK/STAT signaling pathway activation on the transdifferentiation and secretion of transforming growth factor-beta1 (TGF-beta1) induced by high glucose in renal proximal tubular epithelial cells.
  
  
  METHODS
  Human kidney cells (HKC) were cultured and then divided into four groups: low glucose (LG) group, high glucose (HG) group, high mannitol (LG + M) group, and HG + AG490 group. Immunoprecipitation and Western blot analysis were used to determine the expression of tryosine phosphorylated Janus kinase 2 ( p-JAK2). The protein expressions of STAT1, STAT3, p-STAT1, and p-STAT3 and the expressions of alpha-SMA and E-Cadherin were observed by Western blot. The contents of TGF-B1, fibronectin and type I collagen in the supernatants of the cultured HKC were detected by enzyme-linked immunosorbent assay (ELISA). The expression of TGF-beta1 mRNA was measured by reverse transcription and polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Compared with LG group, the expressions of JAK2, p-STAT1, p-STAT3, and TGF-beta1, mRNA were significantly increased in HG group from 6 to 72 hours. Meanwhile, the contents of TGF-beta1 and collagen I in the supernatants and the expression of alpha-SMA increased and the expression of E-Cadherin decreased. The expressions of JAK2, p-STAT1, p-STAT3, and TGF-beta mRNA as well as the levels of TGF-beta1 and collagen I in the supernatant s in HG + AG490 group were significantly lower than in the HG group. The expressions of alpha-SMA and E-Cadherin were also decreased in HG + AG490 group.
  
  
  CONCLUSIONS
  Activation of JAK/STAT signaling pathway may be involved in the high glucose-induced transdifferentiation and overproduction of TGF-beta1, and ECM proteins in HKCs.
authors.affiliation: Department of Nephrology, Tianjin Gongan Hospital, Tianjin 300040, China. zhangmianzhi@vip.sina.com
authors.forename: Mian-zhi
authors.initials: MZ
authors.lastname: Zhang
authors.forename: Min-ying
authors.initials: MY
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.forename: Jian-zhao
authors.initials: JZ
authors.lastname: Duan
authors.forename: Yan-qiu
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Chun-xia
authors.initials: CX
authors.lastname: Zuo
authors.forename: Xiang-yang
authors.initials: XY
authors.lastname: Cheng
authors.forename: Hui-jun
authors.initials: HJ
authors.lastname: Duan
mesh_terms: D002460:Cell Line; D054338:Cell Transdifferentiation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D053612:Janus Kinases / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism; D050791:STAT Transcription Factors / Q000502:physiology*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000378:metabolism; D019459:Urothelium / Q000166:cytology / Q000378:metabolism
chemical_list: D050791:STAT Transcription Factors; D053773:Transforming Growth Factor beta1; D053612:Janus Kinases; D005947:Glucose