Selenium nanoparticles activate selenoproteins to mitigate septic lung injury through miR-20b-mediated RORγt/STAT3/Th17 axis inhibition and enhanced mitochondrial transfer in BMSCs

被引:0
作者
Gu, Wan-Jie [1 ]
Zhao, Feng-Zhi [1 ]
Huang, Wei [1 ]
Zhu, Ming-Gao [1 ]
Huang, Hai-Yan [1 ]
Yin, Hai-Yan [1 ]
Chen, Tianfeng [1 ]
机构
[1] Jinan Univ, Dept Intens Care Unit, Affiliated Hosp 1, Dept Chem,State Key Lab Bioact Mol & Druggabil Ass, Guangzhou, Peoples R China
关键词
Selenium; Acute lung injury; BMSCs; ROR gamma t/STAT3; Th17; Mitochondrial transfer; SEPSIS; CELLS;
D O I
10.1186/s12951-025-03312-2
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Sepsis-induced acute lung injury (ALI) remains a critical clinical challenge with complex inflammatory pathogenesis. While bone marrow mesenchymal stem cells (BMSCs) demonstrate therapeutic potential through anti-inflammatory and cytoprotective effects, their age-related functional decline limits clinical utility. This study developed chitosan-functionalized selenium nanoparticles (SeNPs@CS, 100 nm) to rejuvenate BMSCs through miR-20b-mediated selenoprotein biosynthesis. Mechanistic investigations revealed that SeNPs@CS-treated BMSCs exhibited enhanced mitochondrial transfer capacity, delivering functional mitochondria to damaged alveolar epithelial cells (AECII) for cellular repair. Concurrently, miR-20b upregulation suppressed the ROR gamma t/STAT3/Th17 axis, reducing pro-inflammatory Th17 cell differentiation in CD4+ T lymphocytes. The dual-target mechanism integrates immunomodulation via Th17 pathway inhibition with mitochondrial rejuvenation therapy, representing a paradigm-shifting approach for ALI management. These engineered BMSCs mitigated inflammatory markers in murine models, demonstrating superior efficacy to conventional BMSC therapies. Our findings establish SeNPs@CS-modified BMSCs as a novel therapeutic platform combining nanotechnology-enhanced stem cell engineering with precision immunometabolic regulation, providing new avenues for the treatment of sepsis-induced ALI.
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页数:20
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