Cytosolic phospholipase A2α increases proliferation and de-differentiation of human renal tubular epithelial cells

• Published in: Prostaglandins & other lipid mediators 2016-11, Vol.126, p.1-8
• Main Authors: Montford, John R., Lehman, Allison M.B., Scobey, Micah S., Weiser-Evans, Mary C.M., Nemenoff, Raphael A., Furgeson, Seth B.
• Format: Article
• Language: English
• Subjects: Arachidonic acid; cPLA2α; E-cadherin; HK-2; Phospholipase A2; Proximal tubule
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2016.08.001

•Silencing cPLA2α expression in HK-2 cells alters epithelial morphology and proliferation.•cPLA2α alpha controls E-cadherin promoter activity directly in HK-2 cells.•These effects are mediated by arachidonic acid or cPLA2α itself, and are not dependent on PGE2. The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme controls the release of arachidonic acid from membrane bound phospholipids and is the rate-limiting step in production of eicosanoids. A variety of different kidney injuries activate cPLA2α, therefore we hypothesized that cPLA2α activity would regulate pathologic processes in HK-2 cells, a human renal tubular epithelial cell line, by regulating cell phenotype and proliferation. In two lentiviral cPLA2α-silenced knockdowns, we observed decreased proliferation and increased apoptosis compared to control HK-2 cells. cPLA2α-silenced cells also demonstrated an altered morphology, had increased expression E-cadherin, and decreased expression of Ncadherin. Increased levels of E-cadherin were associated with increased promoter activity and decreased levels of SNAIL1, SNAIL2, and ZEB1, transcriptional repressors of E-cadherin expression. Addition of exogenous arachidonic acid, but not PGE2, reversed the phenotypic changes in cPLA2α-silenced cells. These data suggest that cPLA2α may play a key role in renal repair after injury through a PGE2-independent mechanism.