Downregulation of claudin-2 expression in renal epithelial cells by metabolic acidosis

被引:26
作者
Balkovetz, Daniel F. [1 ,2 ,3 ]
Chumley, Phillip [1 ]
Amlal, Hassane [4 ]
机构
[1] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA
[3] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA
[4] Univ Cincinnati, Coll Med, Dept Med, Cincinnati, OH USA
关键词
paracellular transport; COLLECTING DUCT AQUAPORIN-2; WATER REABSORPTION; PROTEIN ABUNDANCE; TUBULE; TIGHT; RAT; KIDNEY; TRANSPORT; NEPHRON; PATHWAY;
D O I
10.1152/ajprenal.00043.2009
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Balkovetz DF, Chumley P, Amlal H. Downregulation of claudin-2 expression in renal epithelial cells by metabolic acidosis. Am J Physiol Renal Physiol 297: F604-F611, 2009. First published July 8, 2009; doi:10.1152/ajprenal.00043.2009. - Chronic metabolic acidosis (CMA) is associated with an inhibition of fluid reabsorption in the renal proximal tubule. The effects of CMA on paracellular transport across the renal epithelial tight junction (TJ) is unknown. Claudin-2 is a transmembrane TJ-associated protein which confers TJ paracellular permeability to Na+. We examined the effects of CMA on the expression of TJ transport proteins using both in vivo and in vitro models of CMA. The results showed downregulation of claudin-2 mRNA and protein expression in the cortex of rats subjected to the NH4Cl loading model of CMA. Madin-Darby canine kidney (MDCK) and HK-2 cells are models of renal epithelial cells and express claudin-2 protein in their TJ. We examined the effects of acidic pH exposure on the expression of claudin-2 in MDCK and HK-2 renal epithelial cells. Exposure of MDCK cells to pH 6.96 medium caused a significant and reversible decrease in claudin-2 protein abundance. A dose-response analysis of acidic medium exposure of MDCK and HK-2 cells demonstrated a downregulation of claudin-2 protein. The downregulation effect of acidic pH is specific to claudin-2 expression as the expression of other TJ-associated proteins (i.e., claudin-1, -3, -4, and -7, occludin, and zonula occludens-1) remained unchanged compared with control pH (7.40). Collectively, these data demonstrate that CMA downregulates the expression of claudin-2 likely through a direct effect of acidic pH. Potential physiological significance of these changes is discussed.
引用
收藏
页码:F604 / F611
页数:8
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