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Odqvist, L.

Publications and source records attributed to Odqvist, L..

2 recordsLinked to original sources
bioRxiv2026

Extracellular Vesicle microRNAs From Small Airways Promote Senescence and Fibrosis in COPD

BackgroundChronic obstructive pulmonary disease (COPD) is a chronic lung condition characterised by accelerated lung aging. Extracellular vesicles (EVs), which can be categorised into large EVs (LEVs) and small EVs (SEVs), may play a critical role in intercellular communication. They contribute to the pathogenesis of COPD by transporting and transferring microRNAs (miRNAs). This study profiles cells and EV-associated miRNAs from both healthy and COPD small airway (SA)-epithelial cells and SA-fibroblasts and identifies the biological pathways associated with these miRNAs. MethodsEVs were isolated from conditioned media of healthy and COPD SA-epithelial cells and SA-fibroblasts, both at baseline and following H2O2 exposure. MiRNAs were extracted from cells and EVs and analysed by small RNA (smRNA) sequencing. ResultsSmRNA sequencing of COPD SA-epithelial cells and EVs revealed that four miRNAs were upregulated and fourteen were downregulated in the cells compared to healthy controls. COPD LEVs displayed nine upregulated and ten downregulated miRNAs, while SEVs showed ten upregulated and eleven downregulated miRNAs. Only one miRNA consistently upregulated in COPD SA-epithelial cells, LEVs, and SEVs. The various differentially expressed miRNAs were primarily associated with cellular senescence pathways. In SA-fibroblasts 39 miRNAs were upregulated in COPD compared to healthy cells. 14 miRNAs were upregulated in COPD LEVs and 11 downregulated, whereas SEVs exhibited twenty upregulated and eleven downregulated miRNAs. Overlap was limited, with only three miRNAs consistently upregulated in SA-fibroblasts and EVs. These miRNAs were linked to pathways related to fibrosis and cellular senescence. Furthermore, oxidative stress alters the miRNA profiles detected in cells and EVs differently between cells from healthy individuals and COPD patients. ConclusionsCOPD alters miRNA signatures in cells and their EVs, with limited overlap between compartments. These COPD-associated miRNAs are enriched in pathways driving cellular senescence and fibrosis, suggesting a potential role in disease progression.

cell biology↗
bioRxiv2023

Extracellular vesicles propagate aging in COPD airway epithelial cells by transfer of microRNA-34a

RationaleChronic obstructive pulmonary disease (COPD) is associated with the acceleration of lung aging, demonstrated by the accumulation of senescent cells in lung tissue. MicroRNA (miR)-34a is induces senescence by suppressing the key anti-aging molecule, sirtuin-1 (SIRT1). Senescent cells spread senescence to neighboring and distant cells, which favors the progression of COPD and its comorbidities. The mechanisms for spreading senescence remain undetermined but may be mediated by the transfer of microRNAs in extracellular vesicles. ObjectivesTo analyze the miRNA content of extracellular vesicles in COPD and explore their effect on cellular senescence of healthy cells MethodsEVs were isolated from small airway epithelial cells (SAEC) from healthy donors or COPD patients. Recipient healthy SAEC were cultured with EVs and the expression of miR-34a and markers of cellular senescence, p21CIP1 and SIRT1, were measured. Main ResultsEVs from COPD cells induce senescence in healthy recipient cells via the selective transfer of miR-34a. We showed that COPD SAEC produce increased numbers of EVs enriched with miR-34a. EVs are taken up by healthy cells, resulting in reduced expression of the anti-aging molecule sirtuin-1 and increased expression of markers of senescence, such as p21CIP1 and positive staining for senescence-associated {beta}-galactosidase ConclusionsOur findings provide evidence of the mechanism by which EVs spread cellular senescence in human primary cells via miR-34a, rather than via soluble mediators. EVs enriched with miR-34a may spread senescence locally, accounting for disease progression, but also provide a mechanism for distant spread to account for comorbidities and multimorbidity of the elderly.

cell biology↗