[Effect of JAK/STAT pathway activation on high glucose-induced transdifferentiation in renal proximal tubular epithelial cells].
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.
Zhang
Mian-zhi
MZ
Department of Nephrology, Tianjin Gongan Hospital, Tianjin 300040, China. zhangmianzhi@vip.sina.com
Zhang
Min-ying
MY
Zhao
Song
S
Duan
Jian-zhao
JZ
Zhang
Yan-qiu
YQ
Zuo
Chun-xia
CX
Cheng
Xiang-yang
XY
Duan
Hui-jun
HJ
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
D050791:STAT Transcription Factors; D053773:Transforming Growth Factor beta1; D053612:Janus Kinases; D005947:Glucose