Hypoxia stimulates expression of connective tissue growth factor through p38 signaling pathway in human renal interstitial fibroblasts
- VernacularTitle:低氧通过p38丝裂素激活蛋白激酶途径刺激人肾间质成纤维细胞表达结缔组织生长因子
- Author:
Linlin RONG
- Publication Type:Journal Article
- Keywords:
Mitogen-activated protein kinases;
Fibroblasts;
Connective tissue growth factor;
Kidney
- From:
Journal of Peking University(Health Sciences)
2003;0(04):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To assess the expression of connective tissue growth factor (CTGF), and relevant mechanism for the regulation of CTGF expression by hypoxia in human renal interstitial fibroblast. Methods: A human renal interstitial fibroblast cell line TK173 was treated under hypoxia (1%O2) or nomoxia (21%O2) condition. The expressions of HIF1-?, hypoxia marker protein, and CTGF protein were analyzed by Western blotting. PT-PCR was carried out to measure the levels of CTGF mRNA. The activations of MAPKs (ERK, JNK, p38) signaling pathways were assessed at different time points (30 min, 1 h, 6 h, and 12 h ), and the changes of CTGF expression were detected after the inhibitors of activation of MAPKs were applied, respectively. Results: The expression of HIF-1? protein appeared in cells under hypoxia for 6 h. The expressions of CTGF protein were up-regulated in TK173 cells under hypoxia for 12 h, reached the peak levels in 2 folds of normoxia group cells for 24 h, and return to the levels of control cells by 48 h. The levels of CTGF mRNA were elevated in cells under hypoxia for 1 h, significantly increased at 6 h (6.6?1.0,P=0.000 2), and returned to the levels of normoxia group cells by 24 h. Activations of ERK1/2, JNK and p38 were seen in hypoxic cells. Activation of ERK1/2 and JNK were occurred as early as at 10 min, and reached the peak levels at 1 h, while the peak levels of activated JNK were seen at 30 min, then the levels of activated ERK1/2, p38, and JNK were all declined at 6 h, back to the baseline levels at 12 h. Blockade of ERK activation with PD98059, and blockade of JNK activation with SP600125 did not suppress hypoxia-induced expression of CTGF protein, whereas blockade of p38 MARK activation with SB203580 abolished hypoxia-induced expressions of CTGF protein and CTGF mRNA. Conclusion: Hypoxia could stimulate the expression of CTGF in human renal interstitial fibroblast through the activation of p38 MARK signaling pathway.
