High sodium chloride affects BMP-7 and 1α-hydroxylase levels through NCC and CLC-5 in NRK-52E cells
High sodium chloride affects BMP-7 and 1α-hydroxylase levels through NCC and CLC-5 in NRK-52E cells
复制标题
高氯化钠通过 NRK-52E 细胞中的 NCC 和 CLC-5 影响 BMP-7 和 1 α-羟化酶水平
DOI：
10.1016/j.ecoenv.2021.112762
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发表时间：
2021-09-13
影响因子：
6.8
通讯作者：
Zhu, Xiaofeng
中科院分区：
文献类型：
--
作者：
Mo, Shu;Cui, Yan;Zhu, Xiaofeng
高氯化钠（NaCl）的饮食会影响肾功能损害，增加尿钙排泄，导致骨质流失。在肾小管中，Na-Cl共转运蛋白（NCC）和氯离子通道5（CLC-5）参与调节尿钙排泄。此外，肾小管还能合成骨形态发生蛋白7（BMP-7）、1 α-羟化酶等细胞因子，靶向骨组织，对骨代谢起重要作用。然而，NaCl与这些离子通道或细胞因子之间的具体机制仍需要从多方面进行研究。本研究以培养的正常大鼠肾小管上皮细胞NRK-52 E为研究对象，发现高浓度NaCl显著抑制细胞活力，增加细胞凋亡。高浓度NaCl降低骨密度（BMD），如通过NCC和骨桥蛋白（OPN）的mRNA和蛋白水平显著增加所证明的，但降低CLC-5、BMP-7和1 α-羟化酶的水平。此外，我们发现，卵巢切除（OVX）大鼠高盐饮食12周，改变了这些指标在肾皮质的水平。第4、5腰椎和股骨骨密度明显降低，骨微结构破坏。高浓度NaCl可增强对这些细胞因子的抑制作用，这有利于通过调节离子通道NCC和CLC-5诱导的骨密度增加。总之，我们的研究结果表明，高浓度的NaCl通过调节离子通道NCC和CLC-5降低BMD。
A diet high in sodium chloride (NaCl) can affect renal function damage and increase urinary calcium excretion, leading to bone loss. in renal tubules, Na-Cl co-transporter (NCC) and chloride channel 5 (CLC-5) are involved in regulating urinary calcium excretion. In addition, some cytokines, such as Bone morphogenetic protein 7 (BMP-7) and 1 alpha-hydroxylase, are synthesized by renal tubules, which target on bone and play important roles on bone metabolism. However, the specific mechanisms between NaCl and these ion channels or cytokines still need investigations from many aspects. This study, in culture normal rat renal tubular epithelial NRK-52E cells, showed that high concentrations of NaCl significantly inhibited the cell viability and increased the cell apoptosis. High concentration of NaCl reduce bone mineral density (BMD), as demonstrated by the significantly increased mRNA and protein levels of NCC and osteopontin (OPN), but decreased the levels of CLC-5, BMP-7, and 1 alpha-hydroxylase. In addition, we found that ovariectomized (OVX) rats on a high-salt diet for 12 weeks had altered levels of these indices in the renal cortices. Moreover, the BMD in fourth and fifth lumbar vertebra (LV4 and 5) and femurs were significantly decreased and bone microstructure was destroyed of these rats. We also demon-strated that high concentration of NaCl enhanced the inhibition of these cytokines which is beneficial to increase BMD, induced by modulating ion channels NCC and CLC-5. In conclusion, our results indicate that high con-centration of NaCl reduce BMD by regulating ion channels NCC and CLC-5.