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BKCa channels regulate the immunomodulatory properties of WJ-MSCs by affecting the exosome protein profiles during the inflammatory response

BACKGROUND: Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) from the human umbilical cord have been studied extensively due to their immunomodulatory functions. Large-conductance Ca(2+)-activated K(+) (BKCa channels) channels are involved in many inflammatory responses, but their involvemen...

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Detalles Bibliográficos
Autores principales: Song, Ahui, Wang, Jingjing, Tong, Yan, Fang, Junyan, Zhang, Yi, Zhang, Huiping, Ruan, Hongqiang, Wang, Kai, Liu, Yingli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560248/
https://www.ncbi.nlm.nih.gov/pubmed/33059770
http://dx.doi.org/10.1186/s13287-020-01952-9
Descripción
Sumario:BACKGROUND: Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) from the human umbilical cord have been studied extensively due to their immunomodulatory functions. Large-conductance Ca(2+)-activated K(+) (BKCa channels) channels are involved in many inflammatory responses, but their involvement in the anti-inflammatory activity of WJ-MSCs is unknown. The underlying molecular mechanism, through which BKCa channels mediate the immunomodulation of WJ-MSC, which may include changes in exosomes proteomics, has not yet been clarified. METHODS: Alizarin staining, Oil Red O staining, and flow cytometry were used to identify WJ-MSCs, which were isolated from human umbilical cord Wharton’s jelly. BKCa channels were detected in WJ-MSCs using western blotting, real-time polymerase chain reaction (real-time PCR), and electrophysiology, and cytokine expression was examined using real-time PCR and enzyme-linked immunosorbent assays (ELISAs). Exosomes were characterized using transmission electron microscopy and nanoparticle tracking analysis. Proteomics analysis was performed to explore exosomal proteomic profiles. RESULTS: The cells derived from human umbilical cord Wharton’s jelly were identified as MSCs. BKCa channels were detected in the isolated WJ-MSCs, and the expression of these channels increased after lipopolysaccharide (LPS) stimulation. BKCa channels blockade in LPS-treated WJ-MSCs induced apoptosis and decreased interleukin-6 (IL-6) expression. Furthermore, THP-1 cells (human monocytic cell line) stimulated with LPS/interferon gamma (IFN-γ) produced more anti-inflammatory cytokines after treatment with exosomes derived from BKCa channel-knockdown WJ-MSCs (si-exo). We also observed altered expression of mitochondrial ATP synthase alpha subunit (ATP5A1), filamin B, and other proteins in si-exo, which might increase the anti-inflammatory activity of macrophages. CONCLUSIONS: Our study described the functional expression of BKCa channels in WJ-MSCs, and BKCa channels regulated the immunomodulatory properties of WJ-MSCs by affecting the exosomal protein profiles during the inflammatory response.