[Effect of JAK/STAT pathway activation on high glucose-induced transdifferentiation in renal proximal tubular epithelial cells]

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2007 Jun;29(3):364-9.
[Article in Chinese]


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.

Conclusion: 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.

MeSH terms

  • Cell Line
  • Cell Transdifferentiation
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Humans
  • Janus Kinases / physiology*
  • Kidney Tubules, Proximal / cytology*
  • Kidney Tubules, Proximal / metabolism
  • STAT Transcription Factors / physiology*
  • Signal Transduction
  • Transforming Growth Factor beta1 / biosynthesis
  • Transforming Growth Factor beta1 / metabolism
  • Urothelium / cytology
  • Urothelium / metabolism


  • STAT Transcription Factors
  • Transforming Growth Factor beta1
  • Janus Kinases
  • Glucose