Department of Medicine, Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA.
Acta Physiol (Oxf). 2009 Jan;195(1):149-59. doi: 10.1111/j.1748-1716.2008.01929.x. Epub 2008 Oct 28.
The intestinal epithelium engages in bidirectional transport of fluid and electrolytes to subserve the physiological processes of nutrient digestion and absorption, as well as the elimination of wastes, without excessive losses of bodily fluids that would lead to dehydration. The overall processes of intestinal ion transport, which in turn drive the secretion or absorption of water, are accordingly carefully regulated. We and others have identified the epidermal growth factor receptor (EGFr) as a critical regulator of mammalian intestinal ion transport. In this article, we focus on our studies that have uncovered the intricate signalling mechanisms downstream of EGFr that regulate both chloride secretion and sodium absorption by colonocytes. Emphasis will be placed on the EGFr-associated regulatory pathways that dictate the precise outcome to receptor activation in response to signals that may seem, on their face, to be quite similar if not identical. The concepts to be discussed underlie the ability of the intestinal epithelium to utilize a limited set of signalling effectors to produce a variety of outcomes suitable for varying physiological and pathophysiological demands. Our findings therefore are relevant not only to basic biological principles, but also may ultimately point to new therapeutic targets in intestinal diseases where ion transport is abnormal.
肠道上皮细胞进行双向的流体和电解质转运，以支持营养消化和吸收的生理过程，以及废物的清除，而不会导致脱水的体液过度流失。肠道离子转运的整体过程反过来又驱动水的分泌或吸收，因此受到严格的调节。我们和其他人已经确定表皮生长因子受体 (EGFr) 是哺乳动物肠道离子转运的关键调节剂。在本文中，我们重点介绍了我们的研究，这些研究揭示了 EGFr 下游的复杂信号机制，这些机制调节结肠细胞的氯离子分泌和钠离子吸收。重点将放在 EGFr 相关的调节途径上，这些途径决定了受体激活的精确结果，以响应表面上看起来非常相似甚至相同的信号。将要讨论的概念是肠道上皮细胞利用有限的信号效应器产生多种结果的基础，这些结果适合不同的生理和病理生理需求。因此，我们的发现不仅与基本的生物学原理有关，而且最终可能为肠道疾病中离子转运异常的治疗靶点指明方向。
