{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:48:05Z","timestamp":1783651685998,"version":"3.55.0"},"reference-count":29,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K08DK106450"],"award-info":[{"award-number":["K08DK106450"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R03DK117216"],"award-info":[{"award-number":["R03DK117216"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Pediatric Surgical Association","award":["Jay Grosfeld Award"],"award-info":[{"award-number":["Jay Grosfeld Award"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:p>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\/TNF\u03b1), 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.<\/jats:p><jats:p>NEW &amp; 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.<\/jats:p>","DOI":"10.1152\/ajpgi.00195.2019","type":"journal-article","created":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T10:39:50Z","timestamp":1582540790000},"page":"G781-G792","source":"Crossref","is-referenced-by-count":26,"title":["ROCK1 inhibitor stabilizes E-cadherin and improves barrier function in experimental necrotizing enterocolitis"],"prefix":"10.1152","volume":"318","author":[{"given":"Christie","family":"Buonpane","sequence":"first","affiliation":[{"name":"Division of Pediatric Surgery, Ann and Robert H. 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