Nephron. Experimental nephrology · 2006
Connective tissue growth factor is responsible for transforming growth factor-beta-induced peritoneal mesothelial cell apoptosis.
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Szeto Cheuk-Chun, Chow Kai-Ming, Lai Ka-Bik, Szeto Carol Yi-Ki, Kwan Bonnie Ching-Ha, Li Philip Kam-Tao
Аннотация
BACKGROUND: 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.
METHOD: 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.
RESULT: 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, had no effect on the BAX expression.
CONCLUSION: Our results indicate that CTGF is an important downstream mediator of TGF-beta-induced PMC apoptosis.
METHOD: 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.
RESULT: 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, had no effect on the BAX expression.
CONCLUSION: Our results indicate that CTGF is an important downstream mediator of TGF-beta-induced PMC apoptosis.
Предметные рубрики MeSH
AnimalsApoptosisConnective Tissue Growth FactorDown-RegulationEpithelial CellsFibrosisImmediate-Early ProteinsInflammationIntercellular Signaling Peptides and ProteinsPeritoneumProto-Oncogene Proteins c-bcl-2RNA InterferenceRatsRats, Sprague-DawleyTransforming Growth Factor betaUp-Regulationbcl-2-Associated X Protein