Han Song, Wang Guiyun, Qi Xiang, Lee Heung M, Englander Ella W, Greeley George H
Department of Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1832-9. doi: 10.1152/ajpregu.00083.2008. Epub 2008 Mar 26.
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.
阿片肽是APJ受体的内源性配体，阿片肽和APJ在胃肠道中表达。肠道炎症会增加肠道缺氧诱导因子（HIF）和阿片肽的表达。缺氧和炎症是密切相关的细胞损伤因素。这些研究的目的是探讨缺氧对肠道阿片肽表达的影响。将幼鼠暴露于急性缺氧环境中，分别使肝脏、胃十二指肠和结肠的阿片肽mRNA水平升高了10倍、2倍和2倍（与对照组相比，P < 0.05）。缺氧还增加了结肠APJ mRNA水平，在缺氧暴露期间给予阿片肽治疗进一步提高了结肠APJ mRNA水平。体外缺氧也增加了阿片肽和APJ mRNA水平。缺氧诱导的阿片肽表达升高很可能是由HIF介导的，因为HIF激活的阿片肽转录活性依赖于大鼠阿片肽启动子中一个完整的、假定的HIF结合位点。将幼鼠急性暴露于缺氧环境中会降低胃和结肠上皮细胞的增殖；缺氧与阿片肽治疗相结合使上皮细胞增殖增加了50%。在体外，对暴露于缺氧环境的肠道细胞进行阿片肽治疗可增加细胞增殖。在正常氧条件下给予阿片肽治疗无效。我们的研究表明，胃肠道在缺氧和炎症期间阿片肽表达的升高部分起到刺激上皮细胞增殖的作用。
