Scholarlink

Background <p>Idiopathic pulmonary fibrosis (IPF) is characterized by persistent epithelial injury accompanied by mitochondrial dysfunction. Although mesenchymal stem cells (MSCs) can restore epithelial function by donating mitochondria to damaged cells, the molecular mechanisms driving this process remain unclear. In this study, we demonstrate that caveolin-1 (CAV1) enhances mitochondrial transfer from human umbilical-cord-derived MSCs (hucMSCs) to injured epithelial cells.</p> Methods <p>In vitro and in vivo bleomycin-induced models were used to evaluate mitochondrial transfer from hucMSCs to alveolar epithelial cells. Confocal microscopy and intravital lung imaging visualized mitochondrial transfer, while flow cytometry quantified transfer efficiency. Proteomic profiling, mitochondrial functional assays, and lipid analyses were conducted to explore CAV1-associated mechanisms and metabolic outcomes.</p> Results <p>hucMSC treatment restored mitochondrial membrane potential, ATP production, and epithelial cell viability while reducing reactive oxygen species in injured MLE-12 cells. Proteomic analysis showed significant upregulation of CAV1 in hucMSCs cocultured with injured epithelial cells. In the same dataset, differentially expressed proteins were enriched in pathways related to cytoskeletal remodeling and vesicular transport, supporting a role for hucMSC membrane and trafficking dynamics in mitochondrial delivery. Functional validation confirmed that CAV1 overexpression markedly enhanced mitochondrial transfer and restored mitochondrial function, whereas CAV1 knockdown impaired both transfer efficiency and therapeutic outcomes. Mechanistically, transferred mitochondria promoted mitochondria–lipid droplet tethering, boosted fatty acid β-oxidation, and reduced lipid accumulation. CAV1-overexpressing hucMSCs alleviated alveolar epithelial injury and attenuated pulmonary fibrosis.</p> Conclusions <p>Our findings identify CAV1 as a crucial mediator of hucMSC-mediated mitochondrial transfer, which enhances epithelial repair through mitochondrial donation and metabolic reprogramming. These insights provide a mechanistic foundation for optimizing stem cell-based therapies in pulmonary fibrosis.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

CAV1-dependent mitochondrial transfer from hucMSCs reprograms epithelial lipid metabolism to relieve pulmonary fibrosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月19日

查看全文
  • Ye Shao,
  • Jinjin Zhang,
  • Hanchen Liu,
  • Yujie Wang,
  • Bo Liu,
  • Xinglong Yuan,
  • Mengqi Jiang,
  • Changjun Lv,
  • Songzi Zhang,
  • Xiaodong Song,
  • Hongbo Li

摘要

Background

Idiopathic pulmonary fibrosis (IPF) is characterized by persistent epithelial injury accompanied by mitochondrial dysfunction. Although mesenchymal stem cells (MSCs) can restore epithelial function by donating mitochondria to damaged cells, the molecular mechanisms driving this process remain unclear. In this study, we demonstrate that caveolin-1 (CAV1) enhances mitochondrial transfer from human umbilical-cord-derived MSCs (hucMSCs) to injured epithelial cells.

Methods

In vitro and in vivo bleomycin-induced models were used to evaluate mitochondrial transfer from hucMSCs to alveolar epithelial cells. Confocal microscopy and intravital lung imaging visualized mitochondrial transfer, while flow cytometry quantified transfer efficiency. Proteomic profiling, mitochondrial functional assays, and lipid analyses were conducted to explore CAV1-associated mechanisms and metabolic outcomes.

Results

hucMSC treatment restored mitochondrial membrane potential, ATP production, and epithelial cell viability while reducing reactive oxygen species in injured MLE-12 cells. Proteomic analysis showed significant upregulation of CAV1 in hucMSCs cocultured with injured epithelial cells. In the same dataset, differentially expressed proteins were enriched in pathways related to cytoskeletal remodeling and vesicular transport, supporting a role for hucMSC membrane and trafficking dynamics in mitochondrial delivery. Functional validation confirmed that CAV1 overexpression markedly enhanced mitochondrial transfer and restored mitochondrial function, whereas CAV1 knockdown impaired both transfer efficiency and therapeutic outcomes. Mechanistically, transferred mitochondria promoted mitochondria–lipid droplet tethering, boosted fatty acid β-oxidation, and reduced lipid accumulation. CAV1-overexpressing hucMSCs alleviated alveolar epithelial injury and attenuated pulmonary fibrosis.

Conclusions

Our findings identify CAV1 as a crucial mediator of hucMSC-mediated mitochondrial transfer, which enhances epithelial repair through mitochondrial donation and metabolic reprogramming. These insights provide a mechanistic foundation for optimizing stem cell-based therapies in pulmonary fibrosis.

Graphical Abstract