Zelikovic I
Pediatric Nephrology Unit, Rambam Medical Center, Faculty of Medicine, Technion Israel Institute of Technology, P.O.Box 9602, Haifa 31096, Israel.
Pediatr Nephrol. 2001 Nov;16(11):919-35. doi: 10.1007/s004670100671.
Inherited tubular transport disorders comprise a group of diseases that lead to profound derangements in the homeostasis of electrolytes, minerals, or organic solutes in the body. In the past decade remarkable progress has been made in our understanding of the molecular pathogenesis of hereditary tubulopathies and the fundamental molecular physiology of renal tubular transport processes. This review summarizes hereditary diseases caused by mutations in genes encoding transporter or channel proteins operating along the renal tubule. Review of the molecular basis of hereditary tubulopathies reveals various loss-of-function or gain-of-function mutations in genes encoding cotransporter, exchanger, or channel proteins, which are located in the luminal, basolateral, or endosomal membranes of the tubular cell or in paracellular tight junctions. These gene mutations result in a variety of functional defects in transporter/channel proteins, including decreased activity, impaired gating, defective trafficking, impaired endocytosis and degradation, or defective assembly of channel subunits. Further molecular studies of inherited tubular transport disorders may shed more light on the molecular pathophysiology of these diseases and may significantly improve our understanding of the mechanisms underlying renal salt homeostasis, urinary mineral excretion, and blood pressure regulation in health and disease. The identification of the molecular defects in inherited tubulopathies may provide a basis for future design of targeted therapeutic interventions and, possibly, strategies for gene therapy of these complex disorders.
遗传性肾小管转运障碍包括一组导致体内电解质、矿物质或有机溶质稳态严重紊乱的疾病。在过去十年中，我们对遗传性肾小管疾病的分子发病机制以及肾小管转运过程的基本分子生理学的认识取得了显著进展。本综述总结了由沿肾小管发挥作用的转运蛋白或通道蛋白基因突变引起的遗传性疾病。对遗传性肾小管疾病分子基础的综述揭示了编码共转运蛋白、交换蛋白或通道蛋白的基因中存在各种功能丧失或功能获得性突变，这些蛋白位于肾小管细胞的管腔膜、基底外侧膜或内体膜中，或位于细胞旁紧密连接中。这些基因突变导致转运蛋白/通道蛋白出现多种功能缺陷，包括活性降低、门控受损、运输缺陷、内吞和降解受损或通道亚基组装缺陷。对遗传性肾小管转运障碍的进一步分子研究可能会更深入地揭示这些疾病的分子病理生理学，并可能显著增进我们对健康和疾病状态下肾脏盐稳态、尿矿物质排泄及血压调节机制的理解。确定遗传性肾小管疾病中的分子缺陷可能为未来设计靶向治疗干预措施以及可能的这些复杂疾病的基因治疗策略提供基础。
