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The role of ADGRE5/CD97 in human retinal pigment epithelial cell growth and survival
Author(s) -
Eichler Wolfram,
Lohrenz Andrea,
Simon KayUwe,
Krohn Sandra,
Lange Johannes,
Bürger Susanne,
Liebscher Ines
Publication year - 2019
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.14210
Subject(s) - pigment , retinal , microbiology and biotechnology , chemistry , cell growth , biology , biochemistry , organic chemistry
Cell surface molecules of retinal pigment epithelial (RPE) cells participate in the pathogenesis of retinal diseases. In an attempt to identify cell surface proteins that play a role in RPE cell–cell interactions, we have considered studying the expression, regulation, and signaling of ADGRE5/CD97, an adhesion G protein–coupled receptor family member, based on its known adhesive function in other cell types such as leukocytes. We showed that RPE cells express three isoforms of CD97 and identified inflammation‐related cytokines as important mediators regulating CD97 expression. Whereas TNF‐α and IFN‐γ upregulated CD97, TGF‐β decreased CD97 expression. Due to interaction with CD55, ARPE‐19 cells firmly adhered to monocytes and T lymphocytes when overexpressing CD97, suggesting a role for CD97 in controlling leukocyte infiltration across the RPE‐based blood–retinal barrier. CD97‐mediated signaling acted synergistically with PDGF‐BB and IFN‐γ to regulate cell growth and survival, ensuring a cellular balance under inflammatory conditions. These findings suggest that CD97 on RPE cells serves to control leukocyte activation and trafficking in uveoretinal inflammation while at the same time regulating second messenger‐mediated gene expression, cell growth, and survival.