Receptor Signaling and Neutral Endopeptidase are Involved in the Resistance of C-Type Natriuretic Peptide to Human Mesangial Proliferation and Collagen-Iv Expression

Abstract

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-Type Natriuretic Peptide/Natriuretic Peptide Receptor B Regulate the Expression and Secretion of Antibacterial Peptide S100A7 in Goat Mammary Gland Through PKG/JNK/c-Jun Signaling Pathway

“…As for the effects of CNP on cell proliferation and apoptosis, the reports are inconsistent. Recent studies have shown that CNP could inhibit the proliferation and promote apoptosis of many types of cells, including vascular smooth muscle cells [39], renal mesangial cells [40,41], broblasts [42] and endothelial cells [43]. However, CNP promoted the proliferation and inhibited the apoptosis of granulosa cells [44], osteoblasts [45] and Leydig cells [46].…”