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JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Cytosolic phospholipase A 2 α increases proliferation and de-differentiation of human renal tubular epithelial cells.
Prostaglandins & Other Lipid Mediators 2016 November
The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2 α) 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 cPLA2 α, therefore we hypothesized that cPLA2 α 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 cPLA2 α-silenced knockdowns, we observed decreased proliferation and increased apoptosis compared to control HK-2 cells. cPLA2 α-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 cPLA2 α-silenced cells. These data suggest that cPLA2 α may play a key role in renal repair after injury through a PGE2 -independent mechanism.
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