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Updated: Jul 16, 2025
Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
Melatonin Attenuates Sepsis-Induced Acute Lung Injury via Inhibiting Excessive Mitophagy
Jianmin Ling1,2, Shanshan Yu1,2, Feng Xiong1,2
1Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, People's Republic of China.
Background:
Epidemiological studies have indicated that lung injury is a frequent complication of sepsis. Mitophagy is vital to multiple pathological processes and diseases; however, its influence on sepsis-induced acute lung injury remains elusive. Melatonin has multiple antioxidant action and anti-inflammatory effects, including regulating mitophagy and inflammatory cytokine expression. Whereas, little is known about the affection of melatonin and mitophagy on CLP-induced ALI.
Methods:
The in vivo effect of melatonin on OPTN-mediated mitophagy was studied by CLP-induced ALI in a mouse model using C57BL/6 followed by treatment with vehicle and melatonin (30 mg/kg/d, intraperitoneal injection). ALI was assayed by lung wet /dry ratio, hematoxylin and eosin staining, and immunohistochemical staining. Signaling pathway changes were subsequently determined by Western blotting and immunofluorescence staining. The effects of melatonin on STAT3 activation and TNF-α production were detected by Western blotting, PCR, and immunohistochemical staining.
Results:
Our results indicated that OPTN, mitophagy adaptors were significantly repressed in CLP-induced ALI, accompanied by overactivation of mitophagy and inflammation. At the same time, we found that melatonin treatment alleviated ALI caused by CLP, and the effect was highly correlated with OPTN-related mitophagy. Furthermore, we demonstrated that OPTN-related mitophagy, which was normalized by melatonin, blocked STAT3 involved epithelial barrier and inflammation in vivo.
Conclusion:
Overall, our results confirm that mitophagy is adjusted by melatonin in the CLP-induced ALI. Moreover, manipulation of mitophagy through melatonin could be a possible treatment to reduce sepsis-associated lung injury.
Insights
Melatonin treatment alleviates sepsis-induced acute lung injury (ALI) by regulating mitophagy and blocking inflammation. This study highlights melatonin
Area of Science:
- Cellular Biology
- Pathology
- Pharmacology
Background:
- Sepsis frequently causes lung injury.
- Mitophagy's role in sepsis-induced lung injury is unclear.
- Melatonin has antioxidant and anti-inflammatory properties.
Purpose of the Study:
- Investigate melatonin's effect on mitophagy in sepsis-induced acute lung injury (ALI).
- Explore the role of OPTN-mediated mitophagy in ALI.
- Determine melatonin's impact on inflammation and STAT3 signaling.
Main Methods:
- Used a mouse model of CLP-induced ALI.
- Administered melatonin and vehicle.
- Assessed lung injury via wet/dry ratio and histology.
- Analyzed signaling pathways using Western blotting and immunofluorescence.
Main Results:
- CLP-induced ALI repressed OPTN and mitophagy adaptors, increasing inflammation.
- Melatonin treatment alleviated ALI, correlating with normalized OPTN-related mitophagy.
- Melatonin-modulated mitophagy inhibited STAT3 activation and inflammation.
Conclusions:
- Mitophagy is modulated by melatonin in CLP-induced ALI.
- Melatonin's regulation of mitophagy offers a potential therapeutic strategy for sepsis-associated lung injury.
