Al-Awqati Qais
Departments of Medicine and Physiology & Cellular Biophysics, College of Physicians & Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032, USA.
J Am Soc Nephrol. 2008 Mar;19(3):443-9. doi: 10.1681/ASN.2007111195. Epub 2008 Jan 16.
The intercalated cell of the cortical collecting tubule exists in two functional and morphologic forms: alpha cells secrete acid, while beta cells secrete HCO(3). It was found that beta cells convert to alpha type when the animal ingests an acid diet or when isolated perfused tubules are exposed to acid. This conversion of cell phenotype requires the induction of new genes, accompanied by a change in cell shape, development of microvilli, and apical endocytosis. All of these changes are reminiscent of terminal differentiation in epithelial cells. Using a beta intercalated cell line, the cause of this phenotypic change was identified as a new extracellular matrix protein, which was termed hensin. When the action of hensin is blocked, the conversion of beta to alpha intercalated cells is prevented and the animals develop distal renal tubular acidosis. Hensin is expressed in most epithelia, and global knockout of hensin results in embryonic lethality at the time of development of the first columnar epithelium, the visceral endoderm. Furthermore, hensin also seems to be involved in the differentiation of transitional and perhaps stratified epithelia as well. A large number of human carcinomas have deletions in the human ortholog of hensin (DMBT1). Collectively, these studies demonstrate that hensin is a mediator of terminal differentiation in many epithelia.
α细胞分泌酸，而β细胞分泌HCO₃⁻。研究发现，当动物摄入酸性饮食或分离灌注的肾小管暴露于酸性环境时，β细胞会转变为α细胞类型。这种细胞表型的转变需要诱导新基因，同时伴随着细胞形状的改变、微绒毛的发育以及顶端内吞作用。所有这些变化都让人联想到上皮细胞的终末分化。利用β闰细胞系，这种表型变化的原因被确定为一种新的细胞外基质蛋白，命名为hensin。当hensin的作用被阻断时，β闰细胞向α闰细胞的转变被阻止，动物会发生远端肾小管酸中毒。Hensin在大多数上皮中表达，全身性敲除hensin会导致在第一个柱状上皮即脏内胚层发育时胚胎致死。此外，hensin似乎也参与了移行上皮以及可能的复层上皮的分化。大量人类癌症在hensin的人类同源物（DMBT1）中存在缺失。总的来说，这些研究表明hensin是许多上皮中终末分化的介导因子。
