摘要
目的观察JAK/STAT信号途径对高糖诱导肾小管上皮细胞转分化的影响。方法体外培养人肾近曲小管上皮细胞株(HKC),分别给予高糖和JAK抑制剂AG490干预,Western印迹检测α-SMA、E-Cadherin及STAT1、STAT3、p-STAT1和p-STAT3的表达;ELISA法测定上清液中TGF-β1、I型胶原的分泌,RT-PCR检测TGF-β1mRNA表达。结果与低糖组比较,高糖培养的HKC中α-SMA、p-JAK2、p-STAT1和p-STAT3表达明显上调;E-Cadherin表达明显下调;TGF-β1mRNA表达增加;上清液中TGF-β1、Ⅰ型胶原增加。AG490明显抑制α-SMA表达升高,减轻E-Cadherin表达;降低TGF-β1mRNA表达及TGF-β1、Ⅰ型胶原的分泌。结论JAK/STAT信号途径可能参与高糖诱导HKC转分化。
Objective To investigate the effect of activation of JAK/STAT signaling pathway on the transdifferentiation of transforming growth factor-β（TGF-βl） induced by high concentration of glucose in kidney proximal tubular epithelial cells （HKC）. Methods Cultured HKC were treated by high concentration of glucose and JAK inhibitor AG490 to detect the expression of α-SMA, E-Cadberin, STAT1, STAT3, p-STAT1 and p-STAT3 by Western blot and to determine the contents of TGF-β1, fibronectin and type Ⅰ by ELISA and to measure TGF-β1 mRNA expression by RT-PCR. Results The expression of α-SMA, p-JAK2, p-STAT1, p-STAT3 and TGF-β1 mRNA, TGF-β1 and collagen Ⅰ in the supernatants were significantly increased, E-Cadherin expression was significantly downregulated in high concentration of glucose group than those in low concentration of glucose group. AG490 obviously inhibited the increased α-SMA expression, decretmed expressions of E-Cadherin and TGF-β1 mRNA and secretion of TGF-β1 and collagen Ⅰ. Conclusions Activation of JAK/STAT signaling pathway may be involved in the high concentration of glucose-induced HKC transdifferentiation.
出处
《中国老年学杂志》
CAS
CSCD
北大核心
2007年第3期217-220,共4页
Chinese Journal of Gerontology
基金
河北省自然科学基金资助项目(NoC2004000536)
关键词
HKC
转分化
细胞外基质
TGF-Β1
Kidney tubular epithelial cell （HKC）
Transdifferentiation
Extracellular matrix
TGF-β1
