C-type natriuretic peptide suppresses mesangial proliferation and matrix expression via a MMPs/TIMPs-independent pathway in vitro

Abstract

C-type natriuretic peptide (CNP) acts mainly in a local, paracrine fashion to regulate vascular tone and cell proliferation. Although several in vivo studies have demonstrated that CNP exerts an inhibitory effect on mesangial matrix generation, a limited number of reports exist about the anti-extracellular matrix (ECM) accumulation effect of CNP and its underlying mechanisms in mesangial cells (MCs) in vitro. In this 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 h, respectively. CNP administration significantly suppresses MCs proliferation and collagen (Col)-IV expression in a time- and dose-dependent manner. In addition, the study presented herein was designed as a first demonstration of the regulative effects of CNP on the metabolisms of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in MCs in vitro, and found that: (1) CNP administration significantly decreased the secretion and expression of MMP-2 and MMP-9 in the cultured MCs; (2) the secretion and expression of TIMP-1 progressively elevated after treatment with CNP for 24 and 48 h, whereas declined at later time point; (3) CNP expression was negatively correlated with MMP-2 and MMP-9 expression; (4) the balance of MMPs/TIMPs was shifted toward the reduction in MMP-2 and MMP-9 activity and/or the increment in TIMP-1 expression, which could not account for the down-regulation of Col-IV expression in CNP-treated MCs. In conclusion, CNP suppresses mesangial proliferation and ECM expression via a MMPs/TIMPs-independent pathway in vitro.

Targeting Mechanosensitive Piezo1 Alleviated Renal Fibrosis Through p38MAPK-YAP Pathway

“…Thus, targeting the mechanotransduction signaling pathway induced by enhanced ECM stiffness may provide a therapeutic strategy for renal fibrosis. As one of the inherent cells of the kidney, mesangial cells (MCs) have the function of maintaining the metabolic balance of ECM under normal physiological conditions (Huang et al, 2017). MCs can be activated and produce large amounts of ECM in renal fibrosis.…”

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

“…Canaan-Kuhl et al 14 investigated the benefits of CNP infusion (1 µg/kg/min) on the rat model of anti-Thy 1.1 mesangioproliferative nephritis over 7 days and found that the glomerular expression of Col-IV was significantly decreased in the CNP-treated rats to 72 per cent of the buffer controls. Conformably, our latest study also showed that CNP could suppress MCs proliferation and Col-IV expression in vitro 15. However, what on earth receptor signaling and NEP are involved in the resistance of CNP to MCs proliferation and Col-IV expression remains unknown.…”

gga-miR-146c Activates TLR6/MyD88/NF-κB Pathway through Targeting MMP16 to Prevent Mycoplasma Gallisepticum (HS Strain) Infection in Chickens

“…MMPs, a family of zinc-dependent endopeptidases, are of importance in pathological processes, including inflammation, pulmonary diseases, cardiovascular diseases, and cancer. [45,46]. MMP9 promotes Hepatitis B virus replication [47], and is of significant importance in response to gonococcal infection [48].…”

“…The upregulation of miR-155 and miR-21 suppress the NF-κB pathway in HCV- or HIV-infected cells [58]. MiR-17-92 promotes leukemogenesis and activation of the NF-κB signaling [45]. Upregulated miR-429 inhibits the migration of HCC cells via the NF-κB pathway [59].…”