Effects of the MAPK pathway and the expression of CAR in a murine model of viral myocarditis

Abstract

The pathogenesis of viral myocarditis (VMC) is not fully understood. This study aimed to examine the relationship between coxsackie-adenovirus receptor (CAR) and the p38 mitogen activated protein kinase (MAPK) pathway mechanisms in a mouse model. Three groups of mice were established: 5 mice in a control group injected with saline, 15 in the model group injected with coxsackie virus B3 (CVB) and 15 in the intervention group injected with CVB3 but treated with the p38 MAPK inhibitor SB203580. Mice were sacrificed at days 1, 5, 10, 15 and 30 and cardiac tissues were isolated to perform the tests. Quantitative PCR and western blot analysis showed CAR mRNA and protein expression levels were highest in the model group at all time-points (P<0.05). The expression levels of p38 MAPK protein by western blot analysis at days 1, 5 and 10 were obviously higher in the model group (P>0.05). H&E staining used to observe myocardial pathological changes showed the inflammatory infiltration was also higher in the model group at all the time-points (P<0.05). Our results show a direct relationship between CAR and p38 MAPK levels, and since the p38 MAPK inhibitor treatment resulted in reduced levels of CAR as well as lower inflammatory infiltration, it is possible that the signaling pathway may mediate CAR expression during the pathogenesis of VMC.

Low‐intensity pulsed ultrasound attenuates cardiac inflammation of CVB3‐induced viral myocarditis via regulation of caveolin‐1 and MAPK pathways

“…Nakao et al demonstrated that LIPUS affected the inflammatory responses of osteoblasts to LPS, where LPS‐induced production of inflammatory cytokines and phosphorylation of ERK and p38MAPK were decreased by LIPUS treatment . In addition, recent studies indicated that p38 MAPK and ERK signallings played pivotal roles in the pathogenesis of viral myocarditis, and suppressing these signallings led to an inhibition of cardiac injury and benefited the recovery from viral myocarditis . In our study, we also found that p38 MAPK and ERK signallings were activated during viral myocarditis, while LIPUS treatment suppressed these signallings and attenuated the excessive inflammatory response during the disease course.…”

Differential Expression Profiles and Functional Analysis of Circular RNAS in Children with Fulminant Myocarditis

“…Circ 0071542 was predicted to regulate the expression of MAPK by binding hsa-miR-8055. A number of scholars have demonstrated that MAPK participates in the development of myocarditis [38][39][40]. Thus, we speculated that circ 0071542 has a proinflammatory function in fulminant myocarditis by sponging miR-8055 to control MAPK expression.…”

Cepharanthine Suppresses Herpes Simplex Virus Type 1 Replication Through the Downregulation of the PI3K/Akt and p38 MAPK Signaling Pathways

“…The PI3K/AKT and p38 MAPK signaling pathways are critical in cell survival and can be activated by multiple viruses ( Cheng et al, 2020 ; Zhan et al, 2020 ), including rotavirus, varicella-zoster virus (VZV), HIV-1, HSV-1, coxsackievirus B3 (CVB3), Epstein–Barr virus (EBV), severe acute respiratory syndrome (SARS) coronavirus, and hepatitis B virus/hepatitis C virus (HBV/HCV) ( Rahaus et al, 2004 ; Lobeck et al, 2016 ; Niu et al, 2017 ; Zhang et al, 2018 ; Torresi et al, 2019 ; Wang et al, 2019 ; Bouhaddou et al, 2020 ). Activated PI3K/AKT and p38 MAPK can mediate apoptosis, cell differentiation, growth, or immune responses ( Cooray, 2004 ; Sun et al, 2015 ), among which evasion of cell cycle checkpoint regulation and apoptosis inhibition are the major pathways to maintain cell survival and HSV-1 reproduction ( Fehr and Yu, 2013 ; Banerjee et al, 2020 ).…”