Induction of apoptosis in rat hepatic stellate cells by disruption of integrin-mediated cell adhesion.
Cell-matrix adhesion is recognized as a physiologic determinant of cell growth and survival. Integrin occupancy seems to be a primary role. We sought to investigate the signal transduction pathways for integrin effects on cell survival in hepatic stellate cells. Integrin function was antagonized by the soluble integrin recognition sequence pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS) in primary cultures of rat hepatic stellate cells. Integrin antagonism with GRGDS peptide induced apoptosis. To investigate signal transduction mechanisms for the effect of integrins on cell survival in hepatic stellate cells, the expression of p53, Bcl-2, and Bax was analyzed. Incubation with soluble GRGDS peptide resulted in increased expression of p53 and decreased the Bcl-2/Bax ratio. In conclusion, these findings indicate that the abrogation of cell adhesion with soluble GRGDS peptide plays a critical role in the induction of apoptosis of rat hepatic stellate cells.
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
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H
Iwamoto
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Sakai
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Tada
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Nakamuta
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Nawata
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D016023:Integrins; D009842:Oligopeptides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C047981:arginyl-glycyl-aspartic acid