Fas activation induces renal tubular epithelial cell ß8 integrin expression and function in the absence of apoptosis

George Jarad, Bingcheng Wang, Shenaz Khan, Jay DeVore, Hui Miao, Karen Wu, Stephen L. Nishimura, Barbara A. Wible, Martha Konieczkowski, John R. Sedor, Jeffrey R. Schelling

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Cell fate following Fas (CD95) ligand or agonistic anti-Fas antibody stimulation is determined by multiple factors, including Fas expression level, microdomain localization, and modulating cytokines. Highly expressed Fas clusters and activates a canonical apoptosis signaling pathway. In less susceptible cells, Fas transduces apoptosis-independent signals, which are not well defined, but have been linked to inflammation, angiogenesis, and fibrosis. To identify apoptosis-independent Fas pathways, cultured renal tubular epithelial cells were stimulated with agonistic anti-Fas antibodies under conditions that did not cause cell death. Analysis of filter cDNA microarrays revealed β8 integrin subunit mRNA induction in Fasstimulated cells. β8 integrin mRNA expression increased within 3-6 h of Fas ligation due to enhanced mRNA stabilization, and mRNA increases were sustained for 48-72 h. Expression of plasma membrane β8 integrin, as well as its heterodimer partner αv, was increased by Fas activation with a similar kinetic pattern. Fas-induced αvβ8 expression correlated with increased migration to vitronectin, the ligand for αvβ8. Results from studies with function-blocking antibodies against other αvβ integrins or suppression β8 integrin expression by RNA interference demonstrated that induced β8 integrin expression mediated Fas-stimulated migration. We conclude that αvβ8 integrin induction defines an unexpected role for Fas in cell migration, rather than as a cell death receptor.

Original languageEnglish
Pages (from-to)47826-47833
Number of pages8
JournalJournal of Biological Chemistry
Issue number49
StatePublished - Dec 6 2002


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