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10.1152/ajpregu.00566.2013

http://scihub22266oqcxt.onion/10.1152/ajpregu.00566.2013
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suck abstract from ncbi


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pmid24553299      Am+J+Physiol+Regul+Integr+Comp+Physiol 2014 ; 306 (9): R641-6
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  • Heme oxygenase-1 promotes migration and beta-epithelial Na+ channel expression in cytotrophoblasts and ischemic placentas #MMPMID24553299
  • Warrington JP; Coleman K; Skaggs C; Hosick PA; George EM; Stec DE; Ryan MJ; Granger JP; Drummond HA
  • Am J Physiol Regul Integr Comp Physiol 2014[May]; 306 (9): R641-6 PMID24553299show ga
  • Preeclampsia is thought to arise from inadequate cytotrophoblast migration and invasion of the maternal spiral arteries, resulting in placental ischemia and hypertension. Evidence suggests that altered expression of epithelial Na(+) channel (ENaC) proteins may be a contributing mechanism for impaired cytotrophoblast migration. ENaC activity is required for normal cytotrophoblast migration. Moreover, beta-ENaC, the most robustly expressed placental ENaC message, is reduced in placentas from preeclamptic women. We recently demonstrated that heme oxygenase-1 (HO-1) protects against hypertension in a rat model of placental ischemia; however, whether HO-1 regulation of beta-ENaC contributes to the beneficial effects of HO-1 is unknown. The purpose of this study was to determine whether beta-ENaC mediates cytotrophoblast migration and whether HO-1 enhances ENaC-mediated migration. We showed that placental ischemia, induced by reducing uterine perfusion suppressed, and HO-1 induction restored, beta-ENaC expression in ischemic placentas. Using an in vitro model, we found that HO-1 induction, using cobalt protoporphyrin, stimulates cytotrophoblast beta-ENaC expression by 1.5- and 1.8-fold (10 and 50 muM). We then showed that silencing of beta-ENaC in cultured cytotrophoblasts (BeWo cells), by expression of dominant-negative constructs, reduced migration to 56 +/- 13% (P < 0.05) of control. Importantly, HO-1 induction enhanced migration (43 +/- 5% of control, P < 0.05), but the enhanced migratory response was entirely blocked by ENaC inhibition with amiloride (10 muM). Taken together, our results suggest that beta-ENaC mediates cytotrophoblast migration and increasing beta-ENaC expression by HO-1 induction enhances migration. HO-1 regulation of cytotrophoblast beta-ENaC expression and migration may be a potential therapeutic target in preeclamptic patients.
  • |*Cell Movement[MESH]
  • |Animals[MESH]
  • |Cell Line, Tumor[MESH]
  • |Disease Models, Animal[MESH]
  • |Enzyme Induction[MESH]
  • |Epithelial Sodium Channels/genetics/*metabolism[MESH]
  • |Female[MESH]
  • |Heme Oxygenase (Decyclizing)/biosynthesis/*metabolism[MESH]
  • |Heme Oxygenase-1/biosynthesis/*metabolism[MESH]
  • |Humans[MESH]
  • |Ischemia/*enzymology/physiopathology[MESH]
  • |Placenta/*blood supply/*enzymology[MESH]
  • |Placental Circulation[MESH]
  • |Pre-Eclampsia/metabolism/physiopathology[MESH]
  • |Pregnancy[MESH]
  • |RNA Interference[MESH]
  • |Rats[MESH]
  • |Rats, Sprague-Dawley[MESH]
  • |Signal Transduction[MESH]
  • |Transfection[MESH]


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