title: Cytosolic phospholipase A2α increases proliferation and de-differentiation of human renal tubular epithelial cells.
abstract: 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.
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, United States. Electronic address: John.Montford@UCDenver.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Montford
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, United States.
authors.forename: Allison M B
authors.initials: AM
authors.lastname: Lehman
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, United States.
authors.forename: Micah S
authors.initials: MS
authors.lastname: Scobey
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, United States.
authors.forename: Mary C M
authors.initials: MC
authors.lastname: Weiser-Evans
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, United States.
authors.forename: Raphael A
authors.initials: RA
authors.lastname: Nemenoff
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, United States; Denver Health and Hospitals, Denver, CO, United States.
authors.forename: Seth B
authors.initials: SB
authors.lastname: Furgeson
mesh_terms: D016718:Arachidonic Acid / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics; D054337:Cell Dedifferentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020868:Gene Silencing; D054513:Group IV Phospholipases A2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D015820:Cadherins; D016718:Arachidonic Acid; D054513:Group IV Phospholipases A2; D015232:Dinoprostone
keywords: Arachidonic acid; E-cadherin; HK-2; Phospholipase A2; Proximal tubule; cPLA(2)α