The retinoid agonist Tazarotene promotes angiogenesis and wound healing
Therapeutic angiogenesis is a major goal of regenerative medicine, but no clinically approved small molecule exists that enhances new blood vessel formation. Here we show, using a phenotype-driven high-content imaging screen of an annotated chemical library of 1,280 bioactive small molecules, that t...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2016
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| _version_ | 1824459089532420096 |
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| author | Al Haj Zen, A Nawrot, DA Howarth, AL Caporali, A Ebner, D Vernet, A Schneider, JE Bhattacharya, S |
| author_facet | Al Haj Zen, A Nawrot, DA Howarth, AL Caporali, A Ebner, D Vernet, A Schneider, JE Bhattacharya, S |
| author_sort | Al Haj Zen, A |
| collection | OXFORD |
| description | Therapeutic angiogenesis is a major goal of regenerative medicine, but no clinically approved small molecule exists that enhances new blood vessel formation. Here we show, using a phenotype-driven high-content imaging screen of an annotated chemical library of 1,280 bioactive small molecules, that the retinoid agonist Tazarotene, enhances <em>in vitro</em> angiogenesis, promoting branching morphogenesis, and tubule remodeling. The proangiogenic phenotype is mediated by retinoic acid receptor but not retinoic X receptor activation, and is characterized by secretion of the proangiogenic factors hepatocyte growth factor, vascular endothelial growth factor, plasminogen activator, urokinase and placental growth factor, and reduced secretion of the antiangiogenic factor pentraxin-3 from adjacent fibroblasts. <em>In vivo</em>, Tazarotene enhanced the growth of mature and functional microvessels in Matrigel implants and wound healing models, and increased blood flow. Notably, in ear punch wound healing model, Tazarotene promoted tissue repair characterized by rapid ear punch closure with normal-appearing skin containing new hair follicles, and maturing collagen fibers. Our study suggests that Tazarotene, an FDA-approved small molecule, could be potentially exploited for therapeutic applications in neovascularization and wound healing. |
| first_indexed | 2025-02-19T04:36:15Z |
| format | Journal article |
| id | oxford-uuid:63174542-2aa4-4232-a785-cf0e63e67289 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-02-19T04:36:15Z |
| publishDate | 2016 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:63174542-2aa4-4232-a785-cf0e63e672892025-02-04T10:56:44ZThe retinoid agonist Tazarotene promotes angiogenesis and wound healingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:63174542-2aa4-4232-a785-cf0e63e67289EnglishSymplectic Elements at OxfordCell Press2016Al Haj Zen, ANawrot, DAHowarth, ALCaporali, AEbner, DVernet, ASchneider, JEBhattacharya, STherapeutic angiogenesis is a major goal of regenerative medicine, but no clinically approved small molecule exists that enhances new blood vessel formation. Here we show, using a phenotype-driven high-content imaging screen of an annotated chemical library of 1,280 bioactive small molecules, that the retinoid agonist Tazarotene, enhances <em>in vitro</em> angiogenesis, promoting branching morphogenesis, and tubule remodeling. The proangiogenic phenotype is mediated by retinoic acid receptor but not retinoic X receptor activation, and is characterized by secretion of the proangiogenic factors hepatocyte growth factor, vascular endothelial growth factor, plasminogen activator, urokinase and placental growth factor, and reduced secretion of the antiangiogenic factor pentraxin-3 from adjacent fibroblasts. <em>In vivo</em>, Tazarotene enhanced the growth of mature and functional microvessels in Matrigel implants and wound healing models, and increased blood flow. Notably, in ear punch wound healing model, Tazarotene promoted tissue repair characterized by rapid ear punch closure with normal-appearing skin containing new hair follicles, and maturing collagen fibers. Our study suggests that Tazarotene, an FDA-approved small molecule, could be potentially exploited for therapeutic applications in neovascularization and wound healing. |
| spellingShingle | Al Haj Zen, A Nawrot, DA Howarth, AL Caporali, A Ebner, D Vernet, A Schneider, JE Bhattacharya, S The retinoid agonist Tazarotene promotes angiogenesis and wound healing |
| title | The retinoid agonist Tazarotene promotes angiogenesis and wound healing |
| title_full | The retinoid agonist Tazarotene promotes angiogenesis and wound healing |
| title_fullStr | The retinoid agonist Tazarotene promotes angiogenesis and wound healing |
| title_full_unstemmed | The retinoid agonist Tazarotene promotes angiogenesis and wound healing |
| title_short | The retinoid agonist Tazarotene promotes angiogenesis and wound healing |
| title_sort | retinoid agonist tazarotene promotes angiogenesis and wound healing |
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