The Wnt/β-catenin pathway cross-talks with STAT3 signaling to regulate survival of retinal pigment epithelium cells.
Wnt/β-catenin signaling is an essential pathway that regulates numerous cellular processes, including cell survival. The molecular mechanisms contributing to pro-survival Wnt signaling are mostly unknown. Signal transducer and activator of transcription proteins (STATs) are a well-described family of transcription factors. STAT3 induces expression of anti-apoptotic genes in many tissues and is a downstream mediator of protective growth factors and cytokines. In this study, we investigated whether pro-survival Wnt signaling is mediated by STAT3. The Wnt3a ligand activated Wnt signaling in the retinal pigment epithelium ARPE-19 cell line and significantly increased the viability of cells exposed to oxidative stress. Furthermore, Wnt3a increased STAT3 activation and nuclear translocation, as measured by an antibody against phosphorylated STAT3. Reducing STAT3 levels with siRNA eliminated Wnt3a-dependent protection from oxidative stress. Together, these data demonstrate a previously unknown link between Wnt3a-mediated activation of STAT3 and cell survival, and indicate cross-talk between two important pro-survival signaling pathways.
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Miryam A
MA
Fragoso
Amit K
AK
Patel
Rei E I
RE
Nakamura
Hyun
H
Yi
Krishna
K
Surapaneni
Abigail S
AS
Hackam
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000328:Adult; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D020239:Receptor Cross-Talk / Q000187:drug effects*; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D060509:Wnt3A Protein / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism*
D050796:STAT3 Transcription Factor; D060509:Wnt3A Protein; D051176:beta Catenin