Hypoxia Induces Connective Tissue Growth Factor (CTGF) in Cultured Tubular Cells.
- Author:
Young Ki LEE
1
;
Eun Ji KIM
;
Young Ok KIM
;
Hyun Joong KIM
;
Jung Eun LEE
;
Woo Sung HUH
;
Dae Joong KIM
;
Jung Woo NOH
;
Ha Young OH
;
Yoon Goo KIM
Author Information
1. Department of Internal Medicine, Hallym University College of Medicine, Korea.
- Publication Type:Original Article
- Keywords:
Hypoxia;
Connective tissue growth factor;
TGF-beta;
MAP kinase;
Fibrosis
- MeSH:
Animals;
Anoxia*;
Blotting, Northern;
Cell Proliferation;
Connective Tissue Growth Factor*;
Connective Tissue*;
Culture Media, Conditioned;
Enzyme-Linked Immunosorbent Assay;
Fibrosis;
Gene Expression;
Mice;
p38 Mitogen-Activated Protein Kinases;
Phosphotransferases;
Polymerase Chain Reaction;
RNA, Messenger;
Transforming Growth Factor beta;
Transforming Growth Factor beta1
- From:Korean Journal of Nephrology
2005;24(5):729-738
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Connective tissue growth factor (CTGF) is demonstrated to mediate the fibrotic effect of TGF-beta1 and to stimulate cell proliferation and matrix production. In the present study, we examined the effect of hypoxia on CTGF gene expression in cultured mouse tubular cell (MTC). METHODS: Quiescent cultures of MTC were exposed to hypoxia (1% O2) or normoxia in serum-free medium. The effects on hypoxia-induced CTGF expression were evaluated by Northern blot and real- time PCR. The role of MAP kinase was assessed using specific biochemical inhibitors. RESULTS: ELISA revealed that TGF-beta in conditioned medium by MTC exposed to hypoxia was maximally greater at 24 hours (41.16+/-6.31 ng/mL) than medium from normoxic cultures (15.742.92 ng/mL). Hypoxia caused a significant increase in CTGF mRNA expression in MTC (p<0.05). The steady-state level of CTGF mRNA was maximally up regulated by 3-fold within 4 hours as compared with the cells cultured under the normoxic condition. The induction of CTGF was not blocked by either JNK or ERK inhibitor, whereas an inhibitor of p38 MAP kinase reduced the hypoxia-induced stimulation of CTGF (p<0.05). Although hypoxia stimulated TGF-beta production, neutralizing anti-TGF-beta1 antibody did not abolish the hypoxia-induced CTGF mRNA expression. CONCLUSION: These data indicate that hypoxia up-regulates CTGF gene expression, and that p38 MAP kinase plays a role in hypoxic-stimulation of CTGF in cultured renal tubular cells. In addition, hypoxia induces CTGF mRNA expression via a TGF-beta1-independent mechanism.
