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• W3007281531 abstract "Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of newborns. Although incompletely understood, NEC is associated with intestinal barrier dysfunction. E-cadherin, an adherens junction, is a protein complex integral in maintaining normal barrier homeostasis. Rho-associated protein kinase-1 (ROCK1) is a kinase that regulates the E-cadherin complex, and p120-catenin is a subunit of the E-cadherin complex that has been implicated in stabilizing the cadherin complex at the plasma membrane. We hypothesized that E-cadherin is decreased in NEC and that inhibition of ROCK1 would protect against adherens junction disruption. To investigate this, a multimodal approach was used: In vitro Caco-2 model of NEC (LPS/TNFα), rap pup model (hypoxia + bacteria-containing formula), and human intestinal samples. E-cadherin was decreased in NEC compared with controls, with relocalization from the cell border to an intracellular location. ROCK1 exhibited a time-dependent response to disease, with increased early expression in NEC and decreased expression at later time points and disease severity. Administration of ROCK1 inhibitor (RI) resulted in preservation of E-cadherin expression at the cell border, preservation of intestinal villi on histological examination, and decreased apoptosis. ROCK1 upregulation in NEC led to decreased association of E-cadherin to p120 and increased intestinal permeability. RI helped maintain the stability of the E-cadherin-p120 complex, leading to improved barrier integrity and protection from experimental NEC. NEW & NOTEWORTHY This paper is the first to describe the effect of ROCK1 on E-cadherin expression in the intestinal epithelium and the protective effects of ROCK inhibitor on E-cadherin stability in necrotizing enterocolitis." @default.
• W3007281531 created "2020-03-06" @default.
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• W3007281531 date "2020-04-01" @default.
• W3007281531 modified "2023-10-17" @default.
• W3007281531 title "ROCK1 inhibitor stabilizes E-cadherin and improves barrier function in experimental necrotizing enterocolitis" @default.
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• W3007281531 doi "https://doi.org/10.1152/ajpgi.00195.2019" @default.
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