2. Academic Validation
  3. Elevating VAPB-PTPIP51 integration repairs damaged mitochondria-associated endoplasmic reticulum membranes and inhibits lung fibroblasts activation

Elevating VAPB-PTPIP51 integration repairs damaged mitochondria-associated endoplasmic reticulum membranes and inhibits lung fibroblasts activation

  • Int Immunopharmacol. 2025 Feb 6:147:113982. doi: 10.1016/j.intimp.2024.113982.
Jiaqi Ban 1,  Hongru Tian 1,  Yungeng Wei 2,  Lihong Ao 1,  Hequn Gu 1,  Jiamin Zeng 1,  Xiao Peng 1,  Chunyan Ao 1,  Yanzi Zhang 1,  Xiu He 1,  Hua Zhao 1,  Jun Li 3
Affiliations

Affiliations

  • 1 School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, 561113, China.
  • 2 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 3 School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, 561113, China. Electronic address: gygwlj@163.com.
PMID: 39755114 DOI: 10.1016/j.intimp.2024.113982
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.

Keywords

Endoplasmic reticulum stress; Lung fibroblast; Mitochondria-associated endoplasmic reticulum membranes; Mitochondrial damage; VAPB-PTPIP51.

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