Effects of Visfatin on Proliferation and Collagen Synthesis in Rat Cardiac Fibroblasts

Abstract

The proliferation of cardiac fibroblasts (CFs) and excessive extracellular matrix protein accumulation are the basic pathological processes of myocardial fibrosis. Visfatin is a novel adipokine involved in the regulation of inflammatory cytokines, however, the effects of visfatin on proliferation and collagen synthesis of CFs are unclear. The aim of this study was to determine whether visfatin has any effect on the proliferation and collagen synthesis in rat CFs. Incorporation of [ (3)H]-thymidine and [ (3)H]-proline were used for evaluating DNA and collagen synthesis. Flow cytometry techniques were adopted to analyze cell cycle. Enzyme-linked immunosorbent assay was used for measuring collagen type I and III production. RT-PCR and Western blot analysis were used for determining procollagen I and III mRNA expression and protein production. The inhibitors used for pathway determination were: wortmannin [phosphatiylinositol 3-kinase (PI3K)], SB203580 [p38 mitogen-activated protein kinase (MAPK)], PD98059 [extracellular signal-regulated kinase (ERK)1/2)], and JNK inhibitor II [c-Jun NH 2-terminal kinase (JNK)]. We demonstrated that visfatin significantly increased DNA and collagen synthesis in a dose- and time-dependent manner. Cell cycle analysis showed that visfatin increased S-stage percentage and proliferation index in a dose- and time-dependent manner. It was also found that visfatin upregulated collagen I and III production, procollagen I and III mRNA expression and protein production. These effects were diminished by SB203580, wortmannin, and PD98059, but not by JNK inhibitor II. These results suggest that visfatin promote CFs proliferation and collagen synthesis via p38MAPK, PI3K, and ERK 1/2 pathways rather than JNK pathways, which also indicate that visfatin might play a role in myocardial fibrosis.

The role of sirtuin 2 activation by nicotinamide phosphoribosyltransferase in the aberrant proliferation and survival of myeloid leukemia cells

“…The phosphoinositol 3-kinase (PI3K)/AKT pathway is frequently activated in AML, [16][17][18] and it is known that NAMPT induces AKT phosphorylation. 19,20 We did not detect any changes in the levels of phospho-PI3K p85 (Tyr 458) or expression of total PI3K p85 protein in HL-60 cells treated with FK866 or AC93253 compared to DMSO-treated control cells (Online Supplementary Figure S2). However, after inhibition of NAMPT or SIRT2 with FK866 or AC93253 we did find reduced phospho-AKT levels ( Figure 4A).…”

“…NAMPT (visfatin) has recently been shown to induce AKT phosphorylation in endothelial cells and in cardiac fibroblasts. 19,20 AKT phosphorylates and thereby inhibits a serine-threonine kinase glycogen synthase kinase 3β (GSK3β). 21 GSK3β is a well-known inhibitor of Wnt signaling.…”

Modulation of Liver Fibrosis by Adipokines

“…This adipokine was found to stimulate synovial fibroblasts to secrete proinflammatory cytokines and matrix metalloproteinases [50]. More recently, visfatin was reported to increase DNA and collagen synthesis in cardiac fibroblasts, suggesting its role in myocardial fibrosis [51]. Data on hepatic fibrogenesis are awaited.…”

Human perivascular adipose tissue dysfunction as a cause of vascular disease: Focus on vascular tone and wall remodeling

“…These authors suggested a protective role of adiponectin against development of coronary artery diseases. On the other hand, visfatin promotes proliferation of cardiac fibroblasts (Yu et al, 2010) and also upregulate endothelial fibroblast growth factor-2 in human endothelial cells (Bae et al, 2009). …”