Tissue & cell · 2026
Nebulized inhalation of exosomes from human umbilical cord mesenchymal stem cells alleviates bleomycin-induced pulmonary fibrosis through tsRNA cargos.
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Liang Jialong, Zhou Jintao, E Ziqi, Ge Feifan, Zheng Mingfeng, Chen Yuan, Ji Yong
Аннотация
BACKGROUND: Further comprehensive research is needed to elucidate the therapeutic mechanisms of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) in idiopathic pulmonary fibrosis. This study primarily aimed to characterize the tsRNA cargo of hUCMSC-EXOs, identify potential targets through integrated omics analysis, and indicate inhalation of hUCMSC-EXOs can improve bleomycin-induced pulmonary fibrosis.
METHODS: hUCMSC-EXOs were extracted and characterized. The tsRNA cargo of hUCMSC-EXOs was profiled by sequencing, and lung tissue proteomic analysis was performed to identify differentially expressed proteins. Integrated analysis of tsRNA target genes and proteomic data was conducted to identify key targets. As a proof-of-concept evaluation, a bleomycin-induced pulmonary fibrosis mouse model was established, and hUCMSC-EXOs were administered via nebulized inhalation.
RESULTS: Analysis of the top 10 expressed tsRNAs, combined with lung tissue proteomic sequencing, identified four target genes: HSPB1, SOD3, SRSF1, and SRSF6. HSPB1 and SOD3 mainly participate in the VEGF and MAPK signaling pathways. SRSF1 and SRSF6 mainly participate in the IL-17 signaling pathway. In the proof-of-concept in vivo evaluation, treatment with hUCMSC-EXOs improved the fibrotic phenotype and attenuated weight loss in mice.
CONCLUSIONS: This study primarily demonstrated that hUCMSC-EXOs carry tsRNAs that potentially target HSPB1, SOD3, SRSF1, and SRSF6, influencing VEGF, MAPK, and IL-17 signaling pathways. As a proof of concept, nebulized inhalation of hUCMSC-EXOs attenuated bleomycin-induced early fibrotic changes in mice.
METHODS: hUCMSC-EXOs were extracted and characterized. The tsRNA cargo of hUCMSC-EXOs was profiled by sequencing, and lung tissue proteomic analysis was performed to identify differentially expressed proteins. Integrated analysis of tsRNA target genes and proteomic data was conducted to identify key targets. As a proof-of-concept evaluation, a bleomycin-induced pulmonary fibrosis mouse model was established, and hUCMSC-EXOs were administered via nebulized inhalation.
RESULTS: Analysis of the top 10 expressed tsRNAs, combined with lung tissue proteomic sequencing, identified four target genes: HSPB1, SOD3, SRSF1, and SRSF6. HSPB1 and SOD3 mainly participate in the VEGF and MAPK signaling pathways. SRSF1 and SRSF6 mainly participate in the IL-17 signaling pathway. In the proof-of-concept in vivo evaluation, treatment with hUCMSC-EXOs improved the fibrotic phenotype and attenuated weight loss in mice.
CONCLUSIONS: This study primarily demonstrated that hUCMSC-EXOs carry tsRNAs that potentially target HSPB1, SOD3, SRSF1, and SRSF6, influencing VEGF, MAPK, and IL-17 signaling pathways. As a proof of concept, nebulized inhalation of hUCMSC-EXOs attenuated bleomycin-induced early fibrotic changes in mice.