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Elevating VAPB-PTPIP51 integration repairs damaged mitochondria-associated endoplasmic reticulum membranes and
Jiaqi Ban1, Hongru Tian1, Yungeng Wei2
1School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, 561113, China.
Abstract:
Long-term silica exposure to silica dust leads to irreversible pulmonary fibrosis, during which lung fibroblast activation plays an essential role. Mitochondria-associated endoplasmic reticulum membranes (MAMs) is a structural interface for communication between the outer mitochondrial membrane and the endoplasmic reticulum. VAPB-PTPIP51 is a key complex on MAMs. However, the role of VAPB-PTPIP51-linked MAMs in lung fibroblast activation remains under investigation. In this study, we observed mitochondrial damage and endoplasmic reticulum stress in a SiO2-induced lung fibrosis model using C57BL/6J mice. In the model of TGF-β1-induced mouse lung fibroblast (MLG) activation, interventions with Dioscin and TUDCA reduced mitochondrial damage and alleviated endoplasmic reticulum stress by repairing damaged MAMs. Additionally, TUDCA may restore the MAMs structure by enhancing the interaction between VAPB and PTPIP51. Our findings indicate that MAMs may play a crucial role in linking mitochondrial damage and endoplasmic reticulum stress, suggesting their potential involvement in fibroblast activation.
Insights
Silica dust causes lung fibrosis by activating fibroblasts. This study shows that mitochondria-associated endoplasmic reticulum membranes (MAMs) are crucial in this process, and interventions can repair MAMs to alleviate lung damage.
Area of Science:
- Cell Biology
- Pulmonary Medicine
- Toxicology
Background:
- Long-term silica dust exposure causes irreversible pulmonary fibrosis.
- Lung fibroblast activation is a key process in fibrosis development.
- Mitochondria-associated endoplasmic reticulum membranes (MAMs) regulate cell communication and are implicated in cellular stress.
Purpose of the Study:
- To investigate the role of VAPB-PTPIP51-linked MAMs in silica-induced lung fibroblast activation.
- To explore the effects of Dioscin and TUDCA on MAMs in a pulmonary fibrosis model.
Main Methods:
- Induction of a silica (SiO2)-induced lung fibrosis model in C57BL/6J mice.
- Induction of mouse lung fibroblast (MLG) activation using TGF-β1.
- Treatment with Dioscin and TUDCA to assess their impact on mitochondrial damage, endoplasmic reticulum stress, and MAMs.
Main Results:
- Silica exposure led to mitochondrial damage and endoplasmic reticulum stress in the mouse lung fibrosis model.
- Dioscin and TUDCA interventions reduced mitochondrial damage and endoplasmic reticulum stress.
- These interventions repaired damaged MAMs, with TUDCA enhancing VAPB-PTPIP51 interaction.
Conclusions:
- MAMs play a critical role in linking mitochondrial damage and endoplasmic reticulum stress during lung fibroblast activation.
- Repairing MAMs represents a potential therapeutic strategy for pulmonary fibrosis.
