Connective tissue growth factor is responsible for transforming growth factor-beta-induced peritoneal mesothelial cell apoptosis

Nephron. Experimental Nephrology
Cheuk-Chun SzetoPhilip Kam-Tao Li

Abstract

Previous studies found that transforming growth factor-beta (TGF-beta) induces mesothelial production of connective tissue growth factor (CTGF), which may be downstream mediators of TGF-beta. Since high dose TGF-beta induces apoptosis of peritoneal mesothelial cells (PMC), we study the effect of CTGF blockade in the system of TGF-beta-induced PMC apoptosis. We examined the effect of TGF-W in primary culture of rat peritoneal mesothelial cells (PMC). PMC apoptosis was studied by flow cytometry. The effect of CTGF was blocked by antibody and short-interfering RNA (siRNA). Expression of apoptotic gene was studied by real-time polymerase chain reaction. In cultured unstimulated rat PMC, there is a low but definite incidence of spontaneous apoptosis. Stimulation with TGF-beta 50 pg/ml induces an upregulation of apoptotic gene BAX expression and a downregulation of anti-apoptotic gene BCL-2L expression, and a 4-fold increase in PMC apoptosis. The effect of TGF-beta-induced PMC apoptosis was partly prevented by antibody against CTGF, and completely abolished by CTGF-specific siRNA, while CTGF-blockade by siRNA had no effect on PMC necrosis. CTGF silencing by siRNA prevented the down-regulation of BCL-2L expression induced by TGF-beta,...Continue Reading

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Citations

May 9, 2009·Journal of the American Society of Nephrology : JASN·Elsa Sánchez-LópezMarta Ruiz-Ortega
Mar 11, 2009·Differentiation; Research in Biological Diversity·Joanne P KarunaratneNeil C Stickland
May 13, 2008·Cancer Letters·Sabina Sangaletti, Mario P Colombo
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Sep 21, 2006·Molecular Cancer Therapeutics·Nathalie AugerMarie-France Poupon

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