Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, France.
Service de Physiologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, F-75015 Paris, France.
Genes (Basel). 2020 Mar 10;11(3):290. doi: 10.3390/genes11030290.
Claudins are integral proteins expressed at the tight junctions of epithelial and endothelial cells. In the mammalian kidney, every tubular segment express a specific set of claudins that give to that segment unique properties regarding permeability and selectivity of the paracellular pathway. So far, 3 claudins (10b, 16 and 19) have been causally traced to rare human syndromes: variants of cause HELIX syndrome and variants of or cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The review summarizes our current knowledge on the physiology of mammalian tight junctions and paracellular ion transport, as well as on the role of the 3 above-mentioned claudins in health and disease. Claudin 14, although not having been causally linked to any rare renal disease, is also considered, because available evidence suggests that it may interact with claudin 16. Some single-nucleotide polymorphisms of are associated with urinary calcium excretion and/or kidney stones. For each claudin considered, the pattern of expression, the function and the human syndrome caused by pathogenic variants are described.
紧密连接蛋白是一类分布于上皮细胞和内皮细胞间的跨膜蛋白。在哺乳动物肾脏中，每个肾小管节段表达一组特定的紧密连接蛋白，使该节段具有独特的细胞旁途径渗透性和选择性。迄今为止，已有 3 种紧密连接蛋白（10b、16 和 19）被确定与罕见的人类综合征有关：引起 HELIX 综合征的 10b 变体，以及引起家族性低镁血症伴高钙尿和肾钙质沉着症的 16 或 19 变体。该综述总结了我们目前对哺乳动物紧密连接和细胞旁离子转运生理学的认识，以及上述 3 种紧密连接蛋白在健康和疾病中的作用。Claudin 14 虽然没有与任何罕见的肾脏疾病有因果关系，但也被认为与 claudin 16 相互作用，因为现有证据表明它可能与 claudin 16 相互作用。的一些单核苷酸多态性与尿钙排泄和/或肾结石有关。对于每种考虑的紧密连接蛋白，都描述了其表达模式、功能以及致病性变异引起的人类综合征。
