High sodium chloride affects BMP-7 and 1α-hydroxylase levels through NCC and CLC-5 in NRK-52E cells

Autor: Shu Mo, Yan Cui, Kehuan Sun, Haixia Wang, Xunqian Peng, Ling Ou, Xiaojun Lei, Mengtian Huang, Wenhui Mei, Ling Xin, Haibing He, Bojia Peng, Ya Tian, Panpan Wang, Xiaoyun Li, Ronghua Zhang, Xiaofeng Zhu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Ecotoxicology and Environmental Safety, Vol 225, Iss , Pp 112762- (2021)
Druh dokumentu: article
ISSN: 0147-6513
DOI: 10.1016/j.ecoenv.2021.112762
Popis: 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 1α-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 1α-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 demonstrated 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 concentration of NaCl reduce BMD by regulating ion channels NCC and CLC-5.
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