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Peer-reviewedCC BY-NC-NDCell biology and toxicology

HucMSC-EVs attenuate renal fibrosis via miR-874-3p-mediated inhibition of cGAS-STING signaling.

  • Zhuocheng Shi1,2,3
  • Chenxi Jia1,2,3
  • Meiling Chen1,2,3
  • Yihang Yu1,2,3
  • Feng Liu4
  • Deying Zhang5,6,7
  • Guanghui Wei1,2,3
7 affiliations
  1. 1Department of Urology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
  2. 2Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, 400014, China.
  3. 3Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, Chongqing, 400014, China.
  4. 4Department of Pediatric Urology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, China.
  5. 5Department of Urology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. [email protected].
  6. 6Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, 400014, China. [email protected].
  7. 7Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, Chongqing, 400014, China. [email protected].
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Abstract

Chronic kidney disease (CKD) is characterized by progressive renal interstitial fibrosis, which is closely associated with tubular epithelial cell injury, mitochondrial dysfunction, and aberrant inflammatory signaling. Our previous studies demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells (HucMSC-EVs) effectively alleviate renal fibrosis in a unilateral ureteral obstruction (UUO) model. Based on these findings, the present study further investigated the molecular mechanisms underlying the anti-fibrotic effects of HucMSC-EVs. Using a cisplatin-induced HK-2 cell injury model, we evaluated the effects of HucMSC-EVs on epithelial-mesenchymal transition (EMT) and fibrosis. The results showed that HucMSC-EVs attenuated EMT and fibrotic phenotypes in vitro. Consistently, in UUO-induced kidneys, HucMSC-EVs improved renal histopathological injury and alleviated fibrosis. Mechanistically, HucMSC-EVs reduced mitochondrial reactive oxygen species (mtROS) levels and inhibited abnormal opening of the mitochondrial permeability transition pore (mPTP), thereby preserving mitochondrial homeostasis and suppressing activation of the cGAS-STING signaling pathway. The involvement of this pathway was further confirmed using the STING inhibitor C-176. In addition, we validated that miR-874-3p contributes to these protective effects, as its overexpression partially recapitulated the function of HucMSC-EVs. Collectively, these findings suggest that HucMSC-EVs attenuate renal fibrosis by modulating mitochondrial function and inhibiting the cGAS-STING pathway, providing mechanistic insight into EV-mediated protection in kidney injury.

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Cite

BibTeXRIS
BibTeX
@article{shi2026hucmscevs,
  title = {{HucMSC-EVs attenuate renal fibrosis via miR-874-3p-mediated inhibition of cGAS-STING signaling.}},
  author = {Zhuocheng Shi and Chenxi Jia and Meiling Chen and Yihang Yu and Feng Liu and Deying Zhang and Guanghui Wei},
  journal = {Cell biology and toxicology},
  year = {2026},
  month = jul,
  doi = {10.1007/s10565-026-10249-1},
  url = {https://europepmc.org/article/MED/42909641},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - HucMSC-EVs attenuate renal fibrosis via miR-874-3p-mediated inhibition of cGAS-STING signaling.
AU  - Zhuocheng Shi
AU  - Chenxi Jia
AU  - Meiling Chen
AU  - Yihang Yu
AU  - Feng Liu
AU  - Deying Zhang
AU  - Guanghui Wei
PY  - 2026
DA  - 2026/07/28
JO  - Cell biology and toxicology
DO  - 10.1007/s10565-026-10249-1
UR  - https://europepmc.org/article/MED/42909641
AB  - Chronic kidney disease (CKD) is characterized by progressive renal interstitial fibrosis, which is closely associated with tubular epithelial cell injury, mitochondrial dysfunction, and aberrant inflammatory signaling. Our previous studies demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells (HucMSC-EVs) effectively alleviate renal fibrosis in a unilateral ureteral obstruction (UUO) model. Based on these findings, the present study further investigated the molecular mechanisms underlying the anti-fibrotic effects of HucMSC-EVs. Using a cisplatin-induced HK-2 cell injury model, we evaluated the effects of HucMSC-EVs on epithelial-mesenchymal transition (EMT) and fibrosis. The results showed that HucMSC-EVs attenuated EMT and fibrotic phenotypes in vitro. Consistently, in UUO-induced kidneys, HucMSC-EVs improved renal histopathological injury and alleviated fibrosis. Mechanistically, HucMSC-EVs reduced mitochondrial reactive oxygen species (mtROS) levels and inhibited abnormal opening of the mitochondrial permeability transition pore (mPTP), thereby preserving mitochondrial homeostasis and suppressing activation of the cGAS-STING signaling pathway. The involvement of this pathway was further confirmed using the STING inhibitor C-176. In addition, we validated that miR-874-3p contributes to these protective effects, as its overexpression partially recapitulated the function of HucMSC-EVs. Collectively, these findings suggest that HucMSC-EVs attenuate renal fibrosis by modulating mitochondrial function and inhibiting the cGAS-STING pathway, providing mechanistic insight into EV-mediated protection in kidney injury.
SN  - 0742-2091
SN  - 1573-6822
ER  -