有哪些信誉好的足球投注网站active transport of bile acids decreases mucin 2 in neonatal ileum implications for development of necrotizing enterocolitis主动运输的胆汁酸减少粘蛋白2在新生儿坏死性小肠结肠炎回肠影响发展.pdfVIP
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active transport of bile acids decreases mucin 2 in neonatal ileum implications for development of necrotizing enterocolitis主动运输的胆汁酸减少粘蛋白2在新生儿坏死性小肠结肠炎回肠影响发展
Active Transport of Bile Acids Decreases Mucin 2 in
Neonatal Ileum: Implications for Development of
Necrotizing Enterocolitis
Nina A. Martin, Sarah K. Mount Patrick, Teresa E. Estrada, Harrison A. Frisk, Daniel T. Rogan, Bohuslav
Dvorak, Melissa D. Halpern*
Department of Pediatrics and Steele Children’s Research Center, University of Arizona, Tucson, Arizona
Abstract
Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants, but its etiology
remains unclear. We have previously shown that mucin 2 (Muc2) positive goblet cells are significantly decreased in NEC. We
have also shown that ileal bile acids (BAs) are significantly increased during the development of this disease. Because BAs
can affect mucins, we hypothesized that elevated ileal BAs contribute to decreased Muc2 in experimental NEC. The role of
Muc2 in NEC was evaluated in Winnie +/+ mice, a strain that produces aberrant Muc2. Muc2 and trefoil factor 3 (Tff3) were
assessed in neonatal rats subjected to the NEC protocol when bile acids were removed, and in ileal explants from newborn
and older rats cultured with and without BAs. Further, the role of active transport of BAs was determined using neonatal rats
given the apical sodium dependent bile acid transporter (Asbt) inhibitor SC-435 and in neonatal Asbt knockout mice
subjected to the NEC protocol. Mice with aberrant Muc2 had significantly greater incidence and severity of NEC. Using both
in vivo and ex vivo techniques, we determined that BAs decrease Muc2 positive cells in neonatal but not older ileum.
However, Tff3 positive cells are not decreased by BAs. In addition, active transport of BAs is required for BAs to decrease
Muc2 in immature ileum. These data show that functional Muc2 plays a critical role in the prevention of NEC and BAs can
potentiate the decreased Muc2 in disea
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