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<p>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.</p>

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MGRN1 alleviates the progression of obesity-related acute lung injury by protecting lung epithelial cells through restoring mitochondrial function

  • 期刊论文

  • 发表日期：

    2026年7月28日

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  • Yingping Wang,
  • Liming Lu,
  • Hui Jin,
  • Jie Wu,
  • Xin Li,
  • Zhijuan Chen,
  • Lisi Luo

摘要

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.