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2016 ; 126
(ä): 1-8
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Cytosolic phospholipase A(2)? increases proliferation and de-differentiation of
human renal tubular epithelial cells
#MMPMID27554058
Montford JR
; Lehman AM
; Scobey MS
; Weiser-Evans MC
; Nemenoff RA
; Furgeson SB
Prostaglandins Other Lipid Mediat
2016[Nov]; 126
(ä): 1-8
PMID27554058
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The group IVA calcium-dependent cytosolic phospholipase A(2) (cPLA(2)?) 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 cPLA(2)?, therefore we hypothesized that cPLA(2)?
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 cPLA(2)?-silenced knockdowns, we observed decreased proliferation and
increased apoptosis compared to control HK-2 cells. cPLA(2)?-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
cPLA(2)?-silenced cells. These data suggest that cPLA(2)? may play a key role in
renal repair after injury through a PGE(2)-independent mechanism.