Donowitz Mark, Sarker Rafiquel, Lin Ruxian, McNamara George, Tse Chung Ming, Singh Varsha
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Front Physiol. 2022 Jul 19;13:892112. doi: 10.3389/fphys.2022.892112. eCollection 2022.
Use of human enteroids studied in the undifferentiated and differentiated state that mimic the intestinal crypt and villus, respectively, has allowed studies of multiple enterocyte populations, including a large population of enterocytes that are transitioning from the crypt to the villus. This population expresses NHE3, DRA, and CFTR, representing a combination of Na absorptive and anion secretory functions. In this cell population, these three transporters physically interact, which affects their baseline and regulated activities. A study of this cell population and differentiated Caco-2 cells transduced with NHE3 and endogenously expressing DRA and CFTR has allowed an understanding of previous studies in which cAMP seemed to stimulate and inhibit DRA at the same time. Understanding the contributions of these cells to overall intestinal transport function as part of the fasting and post-prandial state and their contribution to the pathophysiology of diarrheal diseases and some conditions with constipation will allow new approaches to drug development.
对处于未分化和分化状态的人肠类器官的研究，分别模拟了肠隐窝和绒毛，这使得对多个肠上皮细胞群体的研究成为可能，包括大量从隐窝向绒毛过渡的肠上皮细胞。这个群体表达NHE3、DRA和CFTR，代表了钠吸收和阴离子分泌功能的组合。在这个细胞群体中，这三种转运蛋白发生物理相互作用，这会影响它们的基线活性和调节活性。对这个细胞群体以及用NHE3转导并内源性表达DRA和CFTR的分化Caco-2细胞的研究，有助于理解先前的研究，在这些研究中，cAMP似乎同时刺激和抑制DRA。了解这些细胞在禁食和餐后状态下对整体肠道转运功能的贡献，以及它们在腹泻性疾病和一些便秘情况的病理生理学中的作用，将为药物开发带来新的方法。
Zotero 插件
