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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/R1832    most recent 00083.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Han, S. Articles by Greeley, G. H. Search for Related Content PubMed PubMed Citation Articles by Han, S. Articles by Greeley, G. H., Jr.

INFLAMMATION AND CYTOKINES

A possible role for hypoxia-induced apelin expression in enteric cell proliferation

Department of Surgery, University of Texas Medical Branch, Galveston, Texas

Submitted 6 February 2008 ; accepted in final form 21 March 2008

Apelin is the endogenous ligand for the APJ receptor, and apelin and APJ are expressed in the gastrointestinal (GI) tract. Intestinal inflammation increases intestinal hypoxia-inducible factor (HIF) and apelin expression. Hypoxia and inflammation are closely linked cellular insults. The purpose of these studies was to investigate the influence of hypoxia on enteric apelin expression. Exposure of rat pups to acute hypoxia increased hepatic, stomach-duodenal, and colonic apelin mRNA levels 10-, 2-, and 2-fold, respectively (P < 0.05 vs. controls). Hypoxia also increased colonic APJ mRNA levels, and apelin treatment during hypoxia exposure enhanced colonic APJ mRNA levels further. In vitro hypoxia also increased apelin and APJ mRNA levels. The hypoxia-induced elevation in apelin expression is most likely mediated by HIF, since HIF-activated apelin transcriptional activity is dependent on an intact, putative HIF binding site in the rat apelin promoter. Acute exposure of rat pups to hypoxia lowered gastric and colonic epithelial cell proliferation; hypoxia in combination with apelin treatment increased epithelial proliferation by 50%. In vitro apelin treatment of enteric cells exposed to hypoxia increased cell proliferation. Apelin treatment during normoxia was ineffective. Our studies imply that the elevation in apelin expression during hypoxia and inflammation in the GI tract functions in part to stimulate epithelial cell proliferation.

inflammation; peptide; rat; gastrointestinal tract

This article has been cited by other articles:

				S. Han, G. Wang, X. Qi, E. W. Englander, and G. H. Greeley Jr. Involvement of a Stat3 binding site in inflammation-induced enteric apelin expression Am J Physiol Gastrointest Liver Physiol, November 1, 2008; 295(5): G1068 - G1078. [Abstract] [Full Text] [PDF]