Developmental regulation of kidney and liver solute carrier and ATP-binding cassette drug transporters and drug metabolizing enzymes: the role of remote organ communication.
Developmental regulation of kidney and liver solute carrier and ATP-binding cassette drug transporters and drug metabolizing enzymes: the role of remote organ communication.
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DOI：
10.1080/17425255.2018.1473376
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发表时间：
2018-06
影响因子：
4.3
通讯作者：
Nigam SK
中科院分区：
文献类型：
--
作者：
Momper JD;Nigam SK
药物转运和代谢的个体发生通常在组织中独立研究，但在出生后不久，转运蛋白和代谢酶的发育调节必须协调。使用遥感和信号转导假说作为一个框架，我们描述了系统生理学的观点如何有助于理解如何通过肝，肾，肠转运蛋白和药物代谢（DME）酶的器官间通信是从出生后到成年期的监管。本文综述了转运蛋白和DME的发育表达和功能模式，重点关注这些蛋白质在肠道，肝脏和肾脏中的相互作用如何在出生后协调，以优化代谢物和内源性信号分子以及肠道微生物组产物的水平。发育表达被认为是遥感和信号转导假说，它解决了转运蛋白和DME如何参与器官间和生物体间的小分子通信的健康，发育和疾病。这一假说得到了越来越多的支持，它与“出生过渡”和出生后发育生理学特别相关，此时器官必须处理与胎儿期不同的关键生理任务，并且远程器官间和可能的生物体间（例如肠道微生物组）通信可能对维持体内平衡至关重要。
The ontogeny of drug transport and metabolism is generally studied independently in tissues, yet in the immediate postnatal period the developmental regulation of transporters and metabolizing enzymes must be coordinated. Using the Remote Sensing and Signaling Hypothesis as a framework, we describe how a systems physiology view helps to make sense of how inter-organ communication via hepatic, renal, and intestinal transporters and drug metabolizing (DMEs) enzymes is regulated from the immediate postnatal period through adulthood. This review examines patterns of developmental expression and function of transporters and DMEs with a focus on how cross-talk between these proteins in the intestine, liver, and kidney may be coordinated postnatally to optimize levels of metabolites and endogenous signaling molecules as well as gut-microbiome products. Developmental expression is considered in terms of the Remote Sensing and Signaling Hypothesis, which addresses how transporters and DMEs participate in inter-organ and inter-organism small molecule communication in health, development, and disease. This hypothesis, for which there is growing support, is particularly relevant to the “birth transition” and post-natal developmental physiology when organs must deal with critical physiological tasks distinct from the fetal period and where remote inter-organ and possibly inter-organismal (e.g. gut microbiome) communication is likely to be critical to maintain homeostasis.
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