Yu Alan S L
aDivision of Nephrology and Hypertension bThe Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, USA.
Curr Opin Nephrol Hypertens. 2017 Sep;26(5):398-404. doi: 10.1097/MNH.0000000000000348.
Paracellular transport across the tight junction is a general mechanism for transepithelial transport of solutes in epithelia, including the renal tubule. However, why paracellular transport evolved, given the existence of a highly versatile system for transcellular transport, is unknown.
Recent studies have identified the paracellular channel, claudin-2, that is responsible for paracellular reabsorption of sodium in the proximal renal tubule. Knockout of claudin-2 in mice impairs proximal sodium and fluid reabsorption but is compensated by upregulation of sodium reabsorption in the loop of Henle. This occurs at the expense of increased renal oxygen consumption, hypoxia of the outer medulla and increased susceptibility to ischemic kidney injury.
Paracellular transport can be viewed as a mechanism to exploit the potential energy in existing electrochemical gradients to drive passive transepithelial transport without consuming additional energy. In this way, it enhances the efficiency of energy utilization by transporting epithelia.
跨紧密连接的细胞旁转运是上皮细胞(包括肾小管)中溶质跨上皮转运的一种普遍机制。然而,鉴于存在高度通用的跨细胞转运系统,细胞旁转运为何会进化尚不清楚。
最近的研究已确定细胞旁通道claudin-2,它负责近端肾小管中钠的细胞旁重吸收。敲除小鼠体内的claudin-2会损害近端钠和液体重吸收,但会通过髓袢中钠重吸收的上调得到补偿。这是以增加肾脏氧消耗、外髓质缺氧以及对缺血性肾损伤易感性增加为代价的。
细胞旁转运可被视为一种利用现有电化学梯度中的势能来驱动被动跨上皮转运而不消耗额外能量的机制。通过这种方式,它提高了转运上皮细胞的能量利用效率。