Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF)  Alleviates Sepsis-Induced Cardiomyopathy by Inhibiting Pyroptosis

Guorong  Liu; Saifeng  Chen; Xiaoyan  Yuan; Guo  Chen; Lei  Xu; Xinmeichen  Meng; Kun  Wu; Dongfeng  Guo

doi:10.18502/ijph.v52i11.14052

Guorong Liu Department of Emergency Medicine, Gongli Hospital, Pudong New Area, Shanghai, China
Saifeng Chen Department of Emergency Medicine, Gongli Hospital, Pudong New Area, Shanghai, China
Xiaoyan Yuan Department of Emergency Medicine, Gongli Hospital, Pudong New Area, Shanghai, China
Guo Chen Department of Emergency Medicine, Gongli Hospital, Pudong New Area, Shanghai, China
Lei Xu Department of Emergency Medicine, Gongli Hospital, Pudong New Area, Shanghai, China
Xinmeichen Meng Department of Emergency Medicine, Gongli Hospital, Pudong New Area, Shanghai, China
Kun Wu Department of Emergency Medicine, Gongli Hospital, Pudong New Area, Shanghai, China
Dongfeng Guo Department of Emergency Medicine, Gongli Hospital, Pudong New Area, Shanghai, China

DOI: https://doi.org/10.18502/ijph.v52i11.14052

Keywords: Sepsis-induced cardiomyopathy; Pyroptosis

Abstract

Background: Sepsis-induced cardiomyopathy (SIC) is a common complication of sepsis accompanied by high prevalence and mortality in sepsis patients. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor, and it exerts critical functions in various diseases, including heart diseases, while its effect on SIC remains elusive. Hence, we aimed to investigate the action of MANF on SIC.

Methods: This study was under the guidance of Gongli Hospital, Shanghai, China from January 2021 to December 2021. H9c2 cells and mice were induced by LPS to establish SIC in vitro and in vivo models. qRT-PCR and Western blot were used to determine gene and protein expressions. The levels of MANF, Interleukin-1β (IL-1β), Interleukin 18 (IL-18), creatine kinase-MB (CK-MB), and cardiac troponin I (cTn I) were detected using ELISA assay. Cell pyroptosis determination was performed by flow cytometry. The DCFDA assay kit was used to determine ROS production.

Results: In SIC in vitro model, LPS induced cell pyroptosis (P<0.001) and ROS accumulation (n (P<0.001). Besides, MANF was decreased in LPS-induced H9c2 cells (P<0.001) and SIC patients (P<0.001). In addition, overexpression of MANF ameliorated SIC-induced injury in H9C2 cells (P<0.001). Furthermore, inhibition of NLRP3 rescued the function of MANF on SIC-induced injury in H9C2 cells (P<0.001). Moreover, enforced MANF suppressed the SIC-induced injury in vivo model (P<0.001).

Conclusion: MANF was down-regulated in SIC. Overexpressed MANF ameliorated the SIC injury by inhibiting NLRP3-mediated pyroptosis.