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Receptor signaling and neutral endopeptidase are involved in the resistance of C-type natriuretic peptide to human mesangial proliferation and collagen-IV expression


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.

  • cell proliferation
  • natriuretic peptides
  • receptors, collagen

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  • Contributors YFW, DDZ and SYL carried out ELISA. GMJ, HHL and YX carried out RT-PCR. YW, JJW and FFL carried out western blot analysis. PH conceived and designed the experiments. CW, BH and WW interpreted the experiments. HHL and PH wrote the manuscript. All authors approved the final version of the manuscript.

  • Funding This study was supported by the National Natural Science Foundation of China (nos. 81570637 and 81000306).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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