MGRN1 alleviates the progression of obesity-related acute lung injury by protecting lung epithelial cells through
Yingping Wang1, Liming Lu2, Hui Jin1
1Emergency Medicine, Kunming Children's Hospital (Children's Hospital Affiliated to Kunming Medical University), Kunming, Yunnan, 650100 China.
Abstract:
Acute lung injury (ALI) is a common respiratory disease worldwide, and obesity is a significant factor contributing to its progression. However, there is still a lack of effective clinical interventions specifically targeting this condition. This study aims to investigate the role of MGRN1 in obesity-related ALI. An obesity-related ALI mouse model was induced by a high-fat diet (HFD) and intratracheal instillation of lipopolysaccharide (LPS). An in vitro model was constructed using palmitic acid (PA) and LPS to stimulate mouse lung epithelial cells (MLE-12). Lung wet/dry weight ratio and HE staining were used to assess pathological changes in lung tissue. Cell damage was evaluated through CCK-8 and LDH release assays. Mitochondrial function was assessed via JC-1, Mito-Tracker Green, MitoSOX Red staining, and ATP content measurement. Additionally, RT-qPCR, Western blot, ELISA, immunofluorescence, and immunohistochemistry were employed to detect the expression of related genes and proteins.MGRN1 is downregulated in obesity-related ALI, and its overexpression alleviates LPS-induced lung histopathological damage in obese mice, reduces TNF-α, IL-1β, IL-6, ROS, and LDH levels, and inhibits PA-LPS-induced MLE-12 cell injury. Additionally, overexpression of MGRN1 restores mitochondrial function in PA-LPS-induced MLE-12 cells and suppresses PINK1/Parkin signaling pathway-mediated mitophagy. Further studies found that treatment with the PINK1 activator MTK458 attenuates the protective effect of MGRN1 overexpression on MLE-12 cells exposed to PA-LPS. MGRN1 restores mitochondrial function by inhibiting PINK1/Parkin-mediated mitophagy, thereby suppressing lung epithelial cell injury and ultimately alleviating obesity-related ALI. These findings suggest that MGRN1 may be a promising therapeutic target and that strategies aimed at restoring MGRN1 or pharmacologically restraining PINK1/Parkin-mediated mitophagy may offer a novel intervention for obese patients at risk of ALI, providing a theoretical basis for future clinical drug development.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s10616-026-01038-z.