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Peer-reviewedCC BY 4.0Biomolecules

Chemokine CXCL12 Mediates Transcription Factor HSF1-Dependent Small Extracellular Vesicle Secretion Through Different Endosomal Stages

  • Yajie Dong1
  • Xiaoyuan Cao1
  • Wenjuan Xie1
  • Xuepeng Fan1
  • Xiaomao Luo1
  • Yi Yan1
  • Jiayin Lu1
  • Haidong Wang1
  1. 1Shanxi Key Laboratory of Animal Disease Research, Prevention and Control, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China
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Abstract

Extracellular vesicles (EVs) serve as key facilitators mediating intercellular communication in skeletal muscle, but the upstream mechanisms regulating their secretion remain incompletely understood. Using proteomic screening, we identified CXCL12 as a candidate HSF1-associated downstream factor. Functional assays showed that CXCL12 promoted C2C12 myoblast proliferation, restrained myogenic differentiation in a stage-dependent manner, and enhanced sEV secretion, accompanied by altered expression of early endosome- and MVB-associated markers. Functionally, CXCL12 knockdown attenuated the HSF1-induced increase in sEV secretion and the upregulation of EEA1 and CD63 protein levels, whereas exogenous recombinant CXCL12 partially restored EEA1 and CD63 expression in the skeletal muscle of muscle-specific HSF1 knockout mice. Collectively, these results are consistent with a model in which CXCL12 is associated with sEV secretion in coordination with changes in early endosome- and MVB-associated protein abundance, suggesting a previously underappreciated role for CXCL12 in vesicle trafficking in the skeletal muscle microenvironment.

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Cite

BibTeXRIS
BibTeX
@article{dong2026chemokine,
  title = {{Chemokine CXCL12 Mediates Transcription Factor HSF1-Dependent Small Extracellular Vesicle Secretion Through Different Endosomal Stages}},
  author = {Yajie Dong and Xiaoyuan Cao and Wenjuan Xie and Xuepeng Fan and Xiaomao Luo and Yi Yan and Jiayin Lu and Haidong Wang},
  journal = {Biomolecules},
  year = {2026},
  month = nov,
  doi = {10.3390/biom16111597},
  url = {https://www.mdpi.com/2218-273X/16/11/1597},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Chemokine CXCL12 Mediates Transcription Factor HSF1-Dependent Small Extracellular Vesicle Secretion Through Different Endosomal Stages
AU  - Yajie Dong
AU  - Xiaoyuan Cao
AU  - Wenjuan Xie
AU  - Xuepeng Fan
AU  - Xiaomao Luo
AU  - Yi Yan
AU  - Jiayin Lu
AU  - Haidong Wang
PY  - 2026
DA  - 2026/11/02
JO  - Biomolecules
DO  - 10.3390/biom16111597
UR  - https://www.mdpi.com/2218-273X/16/11/1597
AB  - Extracellular vesicles (EVs) serve as key facilitators mediating intercellular communication in skeletal muscle, but the upstream mechanisms regulating their secretion remain incompletely understood. Using proteomic screening, we identified CXCL12 as a candidate HSF1-associated downstream factor. Functional assays showed that CXCL12 promoted C2C12 myoblast proliferation, restrained myogenic differentiation in a stage-dependent manner, and enhanced sEV secretion, accompanied by altered expression of early endosome- and MVB-associated markers. Functionally, CXCL12 knockdown attenuated the HSF1-induced increase in sEV secretion and the upregulation of EEA1 and CD63 protein levels, whereas exogenous recombinant CXCL12 partially restored EEA1 and CD63 expression in the skeletal muscle of muscle-specific HSF1 knockout mice. Collectively, these results are consistent with a model in which CXCL12 is associated with sEV secretion in coordination with changes in early endosome- and MVB-associated protein abundance, suggesting a previously underappreciated role for CXCL12 in vesicle trafficking in the skeletal muscle microenvironment.
SN  - 2218-273X
ER  -