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Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway

  • Ying Tan
  • Haichun Ouyang
  • Xiaochan Xiao
  • Jiankai ZhongEmail author
  • Maolong DongEmail author
Original Paper
  • 30 Downloads

Abstract

Irisin plays a protective effect in acute and chronic myocardial damage, but its role in septic cardiomyopathy is unclear. The aim of our study was to explore the in vivo and in vitro effects of irisin using an LPS-induced septic cardiomyopathy model. Our results demonstrated that irisin treatment attenuated LPS-mediated cardiomyocyte death and myocardial dysfunction. At the molecular level, LPS application was associated with mitochondrial oxidative injury, cardiomyocyte ATP depletion and caspase-related apoptosis activation. In contrast, the irisin treatment sustained mitochondrial function by inhibiting DRP1-related mitochondrial fission and the reactivation of mitochondrial fission impaired the protective action of irisin on inflammation-attacked mitochondria and cardiomyocytes. Additionally, we found that irisin modulated DRP1-related mitochondrial fission through the JNK-LATS2 signaling pathway. JNK activation and/or LATS2 overexpression abolished the beneficial effects of irisin on LPS-mediated mitochondrial stress and cardiomyocyte death. Altogether, our results illustrate that LPS-mediated activation of DRP1-related mitochondrial fission through the JNK-LATS2 pathway participates in the pathogenesis of septic cardiomyopathy. Irisin could be used in the future as an effective therapy for sepsis-induced myocardial depression because it corrects DRP1-related mitochondrial fission and normalizes the JNK-LATS2 signaling pathway.

Keywords

Irisin DRP1-related mitochondrial fission JNK-LATS2 signaling pathway 

Notes

Acknowledgements

Thanks for the assistance from PLA general hospital with respect to functional studies in vitro.

Funding

This work is supported by the National Natural Science Foundation of China (NO. 81372055 and NO. 81571895), Natural Science Foundation of Guangdong Province of China (No: 2018A030313067), and Key Specialist Department Training Project of Foshan City, Guangdong Province of China (No: Fspy 3-2015034).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Cell Stress Society International 2019

Authors and Affiliations

  1. 1.Department of Emergency Medicine, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
  2. 2.Department of Cardiology, Shunde HospitalSouthern Medical UniversityFoshanChina
  3. 3.Department of Burns, Nanfang HospitalSouthern Medical UniversityGuangzhouChina

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