MicroRNA-148b targets the TGF-β pathway to regulate angiogenesis and endothelial-to-mesenchymal transition during skin wound healing
Transforming growth factor beta (TGF-β) is crucial for regulation of the endothelial cell (EC) homeostasis. Perturbation of TGF-β signaling leads to pathological conditions in the vasculature, causing cardiovascular disease and fibrotic disorders. The TGF-β pathway is critical in endothelial-to-mese...
| Հիմնական հեղինակներ: | , , , , , , , , , |
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| Ձևաչափ: | Journal article |
| Լեզու: | English |
| Հրապարակվել է: |
Elsevier
2018
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| _version_ | 1826305962173005824 |
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| author | Miscianinov, V Martello, A Rose, L Parish, E Cathcart, B Mitić, T Gray, GA Meloni, M Zen, A Caporali, A |
| author_facet | Miscianinov, V Martello, A Rose, L Parish, E Cathcart, B Mitić, T Gray, GA Meloni, M Zen, A Caporali, A |
| author_sort | Miscianinov, V |
| collection | OXFORD |
| description | Transforming growth factor beta (TGF-β) is crucial for regulation of the endothelial cell (EC) homeostasis. Perturbation of TGF-β signaling leads to pathological conditions in the vasculature, causing cardiovascular disease and fibrotic disorders. The TGF-β pathway is critical in endothelial-to-mesenchymal transition (EndMT), but a gap remains in our understanding of the regulation of TGF-β and related signaling in the endothelium. This study applied a gain- and loss-of function approach and an in vivo model of skin wound healing to demonstrate that miR-148b regulates TGF-β signaling and has a key role in EndMT, targeting TGFB2 and SMAD2. Overexpression of miR-148b increased EC migration, proliferation, and angiogenesis, whereas its inhibition promoted EndMT. Cytokine challenge decreased miR-148b levels in ECs while promoting EndMT through the regulation of SMAD2. Finally, in a mouse model of skin wound healing, delivery of miR-148b mimics promoted wound vascularization and accelerated closure. In contrast, inhibition of miR-148b enhanced EndMT in wounds, resulting in impaired wound closure that was reversed by SMAD2 silencing. Together, these results demonstrate for the first time that miR-148b is a key factor controlling EndMT and vascularization. This opens new avenues for therapeutic application of miR-148b in vascular and tissue repair. |
| first_indexed | 2024-03-07T06:40:44Z |
| format | Journal article |
| id | oxford-uuid:f930875c-a80b-422a-9d83-6deb15c4b33d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:40:44Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:f930875c-a80b-422a-9d83-6deb15c4b33d2022-03-27T12:56:10ZMicroRNA-148b targets the TGF-β pathway to regulate angiogenesis and endothelial-to-mesenchymal transition during skin wound healingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f930875c-a80b-422a-9d83-6deb15c4b33dEnglishSymplectic Elements at OxfordElsevier2018Miscianinov, VMartello, ARose, LParish, ECathcart, BMitić, TGray, GAMeloni, MZen, ACaporali, ATransforming growth factor beta (TGF-β) is crucial for regulation of the endothelial cell (EC) homeostasis. Perturbation of TGF-β signaling leads to pathological conditions in the vasculature, causing cardiovascular disease and fibrotic disorders. The TGF-β pathway is critical in endothelial-to-mesenchymal transition (EndMT), but a gap remains in our understanding of the regulation of TGF-β and related signaling in the endothelium. This study applied a gain- and loss-of function approach and an in vivo model of skin wound healing to demonstrate that miR-148b regulates TGF-β signaling and has a key role in EndMT, targeting TGFB2 and SMAD2. Overexpression of miR-148b increased EC migration, proliferation, and angiogenesis, whereas its inhibition promoted EndMT. Cytokine challenge decreased miR-148b levels in ECs while promoting EndMT through the regulation of SMAD2. Finally, in a mouse model of skin wound healing, delivery of miR-148b mimics promoted wound vascularization and accelerated closure. In contrast, inhibition of miR-148b enhanced EndMT in wounds, resulting in impaired wound closure that was reversed by SMAD2 silencing. Together, these results demonstrate for the first time that miR-148b is a key factor controlling EndMT and vascularization. This opens new avenues for therapeutic application of miR-148b in vascular and tissue repair. |
| spellingShingle | Miscianinov, V Martello, A Rose, L Parish, E Cathcart, B Mitić, T Gray, GA Meloni, M Zen, A Caporali, A MicroRNA-148b targets the TGF-β pathway to regulate angiogenesis and endothelial-to-mesenchymal transition during skin wound healing |
| title | MicroRNA-148b targets the TGF-β pathway to regulate angiogenesis and endothelial-to-mesenchymal transition during skin wound healing |
| title_full | MicroRNA-148b targets the TGF-β pathway to regulate angiogenesis and endothelial-to-mesenchymal transition during skin wound healing |
| title_fullStr | MicroRNA-148b targets the TGF-β pathway to regulate angiogenesis and endothelial-to-mesenchymal transition during skin wound healing |
| title_full_unstemmed | MicroRNA-148b targets the TGF-β pathway to regulate angiogenesis and endothelial-to-mesenchymal transition during skin wound healing |
| title_short | MicroRNA-148b targets the TGF-β pathway to regulate angiogenesis and endothelial-to-mesenchymal transition during skin wound healing |
| title_sort | microrna 148b targets the tgf β pathway to regulate angiogenesis and endothelial to mesenchymal transition during skin wound healing |
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