Effect of JAK/STAT pathway activation on high glucose-induced transdifferentiation in renal proximal tubular epithelial cells / 中国医学科学院学报
Acta Academiae Medicinae Sinicae
; (6): 364-369, 2007.
Article
ي Zh
| WPRIM
| ID: wpr-229973
المكتبة المسؤولة:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
النص الكامل:
1
الفهرس:
WPRIM
الموضوع الرئيسي:
Pharmacology
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Physiology
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Signal Transduction
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Cell Line
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Urothelium
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Bodily Secretions
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Cell Biology
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Epithelial Cells
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STAT Transcription Factors
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Janus Kinases
المحددات:
Humans
اللغة:
Zh
مجلة:
Acta Academiae Medicinae Sinicae
السنة:
2007
نوع:
Article