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Static pressure regulates connective tissue growth factor expression in human mesangial cells
K Hishikawa1, B S Oemar, T Nakaki
1Department of Pharmacology, Teikyo University School of Medicine, Tokyo 173-8605, Japan. hisikawa@med.teikyo-u.ac.jp
The Journal of Biological Chemistry
|March 30, 2001
Summary
High static pressure increases connective tissue growth factor (CTGF) in kidney cells, leading to extracellular matrix buildup and cell death. This suggests CTGF plays a role in high blood pressure-induced kidney damage.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Connective tissue growth factor (CTGF) is implicated in fibrotic disorders like renal fibrosis.
- Mechanical forces, including static pressure, may regulate CTGF expression.
- Renal fibrosis is a common outcome of diverse kidney diseases.
Purpose of the Study:
- To investigate how static pressure affects CTGF gene expression in human mesangial cells.
- To determine the role of CTGF in mediating the effects of high static pressure on mesangial cells.
Main Methods:
- Cultured human mesangial cells were exposed to varying static pressures (40-180 mm Hg).
- CTGF expression, cell proliferation, and apoptosis were assessed.
- CTGF antisense oligonucleotides, TGF-β1 neutralizing antibody, and PKC inhibitors were used.
- DNA microarray analysis was performed to examine gene expression changes.
Main Results:
- Low static pressure (40-80 mm Hg) stimulated proliferation via protein kinase C (PKC).
- High static pressure (100-180 mm Hg) induced apoptosis, reversed by CTGF antisense oligonucleotide.
- High static pressure upregulated CTGF and extracellular matrix proteins (collagen I, IV, laminin).
- Recombinant CTGF induced apoptosis by downregulating anti-apoptotic genes.
Conclusions:
- High blood pressure upregulates CTGF in mesangial cells.
- Elevated CTGF promotes extracellular matrix production and apoptosis.
- CTGF contributes to mesangial remodeling and glomerulosclerosis.