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

The group IVA calcium-dependent cytosolic phospholipase A (cPLAα) 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 cPLAα, therefore we hypothesized that cPLAα 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 cPLAα-silenced knockdowns, we observed decreased proliferation and increased apoptosis compared to control HK-2 cells. cPLAα-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 cPLAα-silenced cells. These data suggest that cPLAα may play a key role in renal repair after injury through a PGE-independent mechanism.