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Claudins in barrier and transport function—the kidney

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Abstract

Claudins are discovered to be key players in renal epithelial physiology. They are involved in developmental, physiological, and pathophysiological differentiation. In the glomerular podocytes, claudin-1 is an important determinant of cell junction fate. In the proximal tubule, claudin-2 plays important roles in paracellular salt reabsorption. In the thick ascending limb, claudin-14, -16, and -19 regulate the paracellular reabsorption of calcium and magnesium. Recessive mutations in claudin-16 or -19 cause an inherited calcium and magnesium losing disease. Synonymous variants in claudin-14 have been associated with hypercalciuric nephrolithiasis by genome-wide association studies (GWASs). More importantly, claudin-14 gene expression can be regulated by extracellular calcium levels via the calcium sensing receptor. In the distal tubules, claudin-4 and -8 form paracellular chloride pathway to facilitate electrogenic sodium reabsorption. Aldosterone, WNK4, Cap1, and KLHL3 are powerful regulators of claudin and the paracellular chloride permeability. The lessons learned on claudins from the kidney will have a broader impact on tight junction biology in other epithelia and endothelia.

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Acknowledgements

This work is supported by grants from National Institute of Diabetes and Digestive and Kidney Diseases—RO1DK084059 and Department of Defense—HDTRA1-11-16-BRCWMDBAA.

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  1. Department of Internal Medicine, Washington University in St. Louis, 660 South Euclid Ave, St. Louis, MO, 63110, USA

    Yongfeng Gong & Jianghui Hou

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Gong, Y., Hou, J. Claudins in barrier and transport function—the kidney. Pflugers Arch - Eur J Physiol 469, 105–113 (2017). https://doi.org/10.1007/s00424-016-1906-6

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  • DOI: https://doi.org/10.1007/s00424-016-1906-6

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