Andrew Audra L, Card Daren C, Ruggiero Robert P, Schield Drew R, Adams Richard H, Pollock David D, Secor Stephen M, Castoe Todd A
Department of Biology, The University of Texas at Arlington, Arlington, Texas;
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado; and.
Physiol Genomics. 2015 May;47(5):147-57. doi: 10.1152/physiolgenomics.00131.2014. Epub 2015 Feb 10.
Snakes provide a unique and valuable model system for studying the extremes of physiological remodeling because of the ability of some species to rapidly upregulate organ form and function upon feeding. The predominant model species used to study such extreme responses has been the Burmese python because of the extreme nature of postfeeding response in this species. We analyzed the Burmese python intestine across a time series, before, during, and after feeding to understand the patterns and timing of changes in gene expression and their relationship to changes in intestinal form and function upon feeding. Our results indicate that >2,000 genes show significant changes in expression in the small intestine following feeding, including genes involved in intestinal morphology and function (e.g., hydrolases, microvillus proteins, trafficking and transport proteins), as well as genes involved in cell division and apoptosis. Extensive changes in gene expression occur surprisingly rapidly, within the first 6 h of feeding, coincide with changes in intestinal morphology, and effectively return to prefeeding levels within 10 days. Collectively, our results provide an unprecedented portrait of parallel changes in gene expression and intestinal morphology and physiology on a scale that is extreme both in the magnitude of changes, as well as in the incredibly short time frame of these changes, with up- and downregulation of expression and function occurring in the span of 10 days. Our results also identify conserved vertebrate signaling pathways that modulate these responses, which may suggest pathways for therapeutic modulation of intestinal function in humans.
由于某些蛇类物种在进食后能够迅速上调器官的形态和功能,因此蛇类为研究极端生理重塑提供了一个独特且有价值的模型系统。用于研究此类极端反应的主要模型物种是缅甸蟒,因为该物种进食后的反应具有极端性。我们分析了缅甸蟒在进食前、进食期间和进食后的整个时间序列中的肠道情况,以了解基因表达变化的模式和时间,以及它们与进食后肠道形态和功能变化的关系。我们的结果表明,超过2000个基因在进食后小肠中的表达出现显著变化,包括参与肠道形态和功能的基因(如水解酶、微绒毛蛋白、运输和转运蛋白),以及参与细胞分裂和凋亡的基因。基因表达的广泛变化惊人地迅速,在进食后的前6小时内发生,与肠道形态的变化同时出现,并在10天内有效恢复到进食前的水平。总体而言,我们的结果以前所未有的方式描绘了基因表达、肠道形态和生理学的平行变化,这种变化在幅度和变化时间框架上都极为极端,基因表达和功能的上调和下调在10天内发生。我们的结果还确定了调节这些反应的保守脊椎动物信号通路,这可能为人类肠道功能的治疗性调节提供途径。