C-Type Natriuretic Peptide Dampens Fibroblast Growth Factor-23 Expression Through MAPK Signaling Pathway in Human Mesangial Cells
C-Type Natriuretic Peptide Dampens Fibroblast Growth Factor-23 Expression Through MAPK Signaling Pathway in Human Mesangial Cells
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C 型利钠肽通过 MAPK 信号通路抑制人系膜细胞中成纤维细胞生长因子 23 的表达。
DOI：
10.1089/jir.2018.0051
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发表时间：
2018-11-01
影响因子：
2.3
通讯作者：
Hu，Peng
中科院分区：
文献类型：
--
作者：
Wu，Yang Fang;Zhang，Dong Dong;Hu，Peng
C 型利钠肽 (CNP) 被认为是在肾脏局部产生的，具有多种肾脏保护特性。相比之下，成纤维细胞生长因子 (FGF) -23 在慢性肾病的早期阶段会升高并预测其结果。目前，多项研究表明CNP与FGF-23通过紧密的通路发挥作用，并且CNP可明显抑制FGF-23/丝裂原激活蛋白激酶(MAPK)。在本研究中，在不存在或存在 CNP（0、10 和 100 pM）的情况下，将人系膜细胞 (MC) 在含血清培养基中分别孵育 24、48 和 72 小时。 CNP 给药以时间和剂量依赖性方式显着抑制 MC 增殖。作为 CNP 激活的下游信号，经 CNP 处理后，MC 中利钠肽受体 (NPR)-B、环鸟苷单磷酸依赖性蛋白激酶 II 和 NPR-C 的表达明显增强，而中性内肽酶表达显着降低。在整个观察期间，使用不同剂量的 CNP 的 MC 中 FGF-23、FGF 受体 1 和 RAF-1 经历了显着的下调。 CNP 可能通过 MAPK 信号通路抑制 MC 中 FGF-23 的表达。
C-type natriuretic peptide (CNP) is believed to be produced locally in the kidneys and possess several renoprotective properties. In contrast, fibroblast growth factor (FGF) -23 elevates in the early stage of chronic kidney disease and predicts its outcomes. Currently, several studies have demonstrated that CNP and FGF-23 act through a close pathway, and moreover, FGF-23/mitogen-activated protein kinase (MAPK) can be obviously suppressed by CNP. In the present study, human mesangial cells (MCs) were incubated in serum-containing medium in the absence or presence of CNP (0, 10 and 100 pM) for 24, 48 and 72 h, respectively. CNP administration significantly suppresses MCs proliferation in a time- and dose-dependent manner. As a down-stream signaling of CNP activation, the expressions of natriuretic peptide receptor (NPR)-B, cyclic guanosine monophosphate-dependent protein kinases II and NPR-C were obviously augmented, whereas neutral endopeptidase expression was significantly decreased after CNP treatment in MCs. FGF-23, FGF receptor-1 and RAF-1 experienced a pronounced down-regulation in MCs with different doses of CNP throughout the whole observational period. CNP may dampen FGF-23 expression via MAPK signaling pathway in MCs.