Inhibition of visfatin alleviates sepsis-induced intestinal damage by inhibiting Hippo signaling pathway

Abstract

Background The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism. Methods C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines. Results The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866. Conclusion In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.

Oleanolic acid, a small-molecule natural product, inhibits ECM degeneration in osteoarthritis by regulating the Hippo/YAP and Wnt/β-catenin pathways

“…The Yap–Hippo signaling pathway inhibitor XMU-MP-1 (1 μM; MedChemExpress, USA) 45 was used to further verify the mechanism of action of OLA on the protection of chondrocytes. As shown in Fig.…”

“…To clarify the role of OLA in the YAP-Hippo signaling pathway, we detected the levels of key genes and proteins in the pathway after intervention with different doses of OLA. As shown in The Yap-Hippo signaling pathway inhibitor XMU-MP-1 (1 μM; MedChemExpress, USA) 45 was used to further verify the mechanism of action of OLA on the protection of chondrocytes. As shown in Fig.…”

Predictive value of adipokines for the severity of acute pancreatitis: a meta-analysis

“…However, it is still unclear whether leptin and adiponectin have different effects at different stages of inflammation, or whether an imbalance among leptin, adiponectin and other adipokines may inhibit their regulation of the immune response, or whether there are other possible mechanisms, which need to be confirmed by more studies. Although most studies show that visfatin appears to have pro-inflammatory effects [ 33 – 35 , 59 – 62 ], there are some studies that show the opposite [ 29 , 30 , 63 ]. In response to this seemingly contradictory result, the study by Sayers et al may give us some insight.…”

Predictive value of adipokines for the severity of acute pancreatitis: a meta-analysis

“…Visfatin has nicotinamide phosphoribose transferase (Nampt) activity, the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD) remedial synthesis pathway, and macrophages rely on the NAD remedial pathway to meet their energy requirements and maintain their proinflammatory phenotype, and visfatin promotes the release of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α from peripheral monocytes [17][18][19]. Interestingly, visfatin appears to have antiinflammatory [42][43][44] as well as pro-inflammatory effects [17][18][19][45][46][47][48]. In response to this seemingly contradictory result, the study by Sayers et al may give us some insight.…”