Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin

The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. BALB/c m...

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Veröffentlicht in:PloS one 2015-07, Vol.10 (7), p.e0132031-e0132031
Hauptverfasser: Lai, Yu, Zhong, Wa, Yu, Tao, Xia, Zhong-Sheng, Li, Jie-Yao, Ouyang, Hui, Shan, Ti-Dong, Yang, Hong-Sheng, Chen, Qi-Kui
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container_title PloS one
container_volume 10
creator Lai, Yu
Zhong, Wa
Yu, Tao
Xia, Zhong-Sheng
Li, Jie-Yao
Ouyang, Hui
Shan, Ti-Dong
Yang, Hong-Sheng
Chen, Qi-Kui
description The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05). Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.
doi_str_mv 10.1371/journal.pone.0132031
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In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. COX expression was significantly down-regulated in aspirin induced SII (P &lt; 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P &lt; 0.05). Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0132031</identifier><identifier>PMID: 26135128</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accumulation ; Alanine - analogs &amp; derivatives ; Alanine - pharmacology ; Animal tissues ; Animals ; Anti-inflammatory agents ; Anti-Inflammatory Agents, Non-Steroidal - toxicity ; Aspirin ; Aspirin - toxicity ; beta Catenin - biosynthesis ; beta Catenin - genetics ; beta Catenin - physiology ; Body Weight - drug effects ; c-Myc protein ; Cardiovascular disease ; Cell Division - drug effects ; Cyclooxygenase 2 - biosynthesis ; Cyclooxygenase 2 - genetics ; Cyclooxygenase-2 ; Dinoprostone - biosynthesis ; Drugs ; Enzyme immunoassay ; Epithelial cells ; Female ; Gastroenterology ; Gene expression ; Immunoassay ; Inflammation ; Injuries ; Intestinal Absorption - drug effects ; Intestinal Mucosa - drug effects ; Intestinal Mucosa - physiology ; Intestinal Mucosa - ultrastructure ; Jejunum - drug effects ; Jejunum - physiology ; Jejunum - ultrastructure ; Laboratory animals ; Maintenance ; Male ; Membrane Proteins - biosynthesis ; Mice ; Mice, Inbred BALB C ; mRNA ; Mucosa ; Myc protein ; Nonsteroidal anti-inflammatory drugs ; Pathogenesis ; Permeability ; Proliferating cell nuclear antigen ; Prostaglandin E2 ; Proto-Oncogene Proteins c-myc - biosynthesis ; Quinolones - pharmacology ; Random Allocation ; Regeneration ; Regeneration - drug effects ; RNA, Messenger - biosynthesis ; Rodents ; Small intestine ; Studies ; Tight junctions ; Tight Junctions - drug effects ; Zonula occludens-1 protein ; β-Catenin</subject><ispartof>PloS one, 2015-07, Vol.10 (7), p.e0132031-e0132031</ispartof><rights>2015 Lai et al. 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In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. COX expression was significantly down-regulated in aspirin induced SII (P &lt; 0.05). 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lai, Yu</au><au>Zhong, Wa</au><au>Yu, Tao</au><au>Xia, Zhong-Sheng</au><au>Li, Jie-Yao</au><au>Ouyang, Hui</au><au>Shan, Ti-Dong</au><au>Yang, Hong-Sheng</au><au>Chen, Qi-Kui</au><au>Tasken, Kjetil</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-07-02</date><risdate>2015</risdate><volume>10</volume><issue>7</issue><spage>e0132031</spage><epage>e0132031</epage><pages>e0132031-e0132031</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. COX expression was significantly down-regulated in aspirin induced SII (P &lt; 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P &lt; 0.05). Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26135128</pmid><doi>10.1371/journal.pone.0132031</doi><oa>free_for_read</oa></addata></record>
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1932-6203
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subjects Accumulation
Alanine - analogs & derivatives
Alanine - pharmacology
Animal tissues
Animals
Anti-inflammatory agents
Anti-Inflammatory Agents, Non-Steroidal - toxicity
Aspirin
Aspirin - toxicity
beta Catenin - biosynthesis
beta Catenin - genetics
beta Catenin - physiology
Body Weight - drug effects
c-Myc protein
Cardiovascular disease
Cell Division - drug effects
Cyclooxygenase 2 - biosynthesis
Cyclooxygenase 2 - genetics
Cyclooxygenase-2
Dinoprostone - biosynthesis
Drugs
Enzyme immunoassay
Epithelial cells
Female
Gastroenterology
Gene expression
Immunoassay
Inflammation
Injuries
Intestinal Absorption - drug effects
Intestinal Mucosa - drug effects
Intestinal Mucosa - physiology
Intestinal Mucosa - ultrastructure
Jejunum - drug effects
Jejunum - physiology
Jejunum - ultrastructure
Laboratory animals
Maintenance
Male
Membrane Proteins - biosynthesis
Mice
Mice, Inbred BALB C
mRNA
Mucosa
Myc protein
Nonsteroidal anti-inflammatory drugs
Pathogenesis
Permeability
Proliferating cell nuclear antigen
Prostaglandin E2
Proto-Oncogene Proteins c-myc - biosynthesis
Quinolones - pharmacology
Random Allocation
Regeneration
Regeneration - drug effects
RNA, Messenger - biosynthesis
Rodents
Small intestine
Studies
Tight junctions
Tight Junctions - drug effects
Zonula occludens-1 protein
β-Catenin
title Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin
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