Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Gastroenterology, Anhui Provincial Children's Hospital, Anhui Medical University, Hefei, China.
J Investig Med. 2018 Jun;66(5):1-9. doi: 10.1136/jim-2017-000533. Epub 2018 Jan 23.
C-type natriuretic peptide (CNP) is regarded as a local, paracrine hormone to regulate vascular tone and cell proliferation. Although several in vivo studies have documented that CNP exerts the inhibitory effects on mesangial cells (MCs) proliferation and collagen production, a limited number of studies exist about the resistance of CNP to MCs proliferation in vitro. Besides, whether its receptor signaling and neutral endopeptidase (NEP) are involved remains unclear. In the present study, human MCs were incubated in serum-containing medium in the absence or presence of CNP (0, 10 and 100 pM) for 24, 48 and 72 hours, respectively. CNP administration significantly suppresses MCs proliferation and collagen-IV (Col-IV) expression in a time-dependent and dose-dependent manner. As a down-stream signal molecule 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 NEP expression was significantly decreased after CNP treatment. In conclusion, receptor signaling and NEP are involved in the resistance of CNP to human mesangial proliferation and Col-IV expression.
C 型利钠肽（CNP）被认为是一种局部、旁分泌激素，可调节血管张力和细胞增殖。尽管有几项体内研究表明 CNP 对系膜细胞（MCs）增殖和胶原产生具有抑制作用，但关于 CNP 在体外对 MCs 增殖的抗性的研究数量有限。此外，其受体信号和中性内肽酶（NEP）是否参与其中仍不清楚。在本研究中，将人 MCs 在含血清的培养基中孵育，分别在无 CNP（0、10 和 100 pM）或存在 CNP 的情况下孵育 24、48 和 72 小时。CNP 给药可显著抑制 MCs 的增殖和胶原-IV（Col-IV）表达，呈时间和剂量依赖性。作为 CNP 激活的下游信号分子，利钠肽受体（NPR）-B、环鸟苷酸依赖性蛋白激酶 II 和 NPR-C 的表达明显增加，而 CNP 处理后 NEP 的表达明显降低。总之，受体信号和 NEP 参与了 CNP 对人系膜增殖和 Col-IV 表达的抗性。
