Role of Thrombospondin-1 and Nuclear Factor-κB Signaling Pathways in Antiangiogenesis of Infantile Hemangioma
Propranolol is the first-line drug for treatment of infantile hemangioma. However, its mechanism of action remains unclear. Nuclear factor-κB is highly expressed in tumors, directly or indirectly promoting angiogenesis. Thrombospondin-1 is the most important antiangiogenesis protein in vivo. These p...
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| Veröffentlicht in: | Plastic and reconstructive surgery (1963) 2018-09, Vol.142 (3), p.310e-321e |
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| container_title | Plastic and reconstructive surgery (1963) |
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| creator | Xu, Weili Li, Suolin Yu, Fengxue Zhang, Yongting Yang, Xiaofeng An, Wenting Wang, Wenbo Sun, Chi |
| description | Propranolol is the first-line drug for treatment of infantile hemangioma. However, its mechanism of action remains unclear. Nuclear factor-κB is highly expressed in tumors, directly or indirectly promoting angiogenesis. Thrombospondin-1 is the most important antiangiogenesis protein in vivo. These proteins mediate signaling pathways, probably playing an important role in hemangioma treatment. This study explored the synergistic regulation of thrombospondin-1 and nuclear factor-κB signaling pathways in the treatment of hemangioma with propranolol.
The hemangioma-derived endothelial cells were sorted out from the specimens of proliferative hemangioma by flow cytometry. Furthermore, a BALB/c nude mouse hemangioma model was established. Viability and proliferation of hemangioma-derived endothelial cells and the role of thrombospondin-1 and nuclear factor-κB signaling pathways were observed after propranolol administration in vitro and in vivo.
The expression of thrombospondin-1 and its receptor CD36 in hemangioma-derived endothelial cells gradually increased with the increase in propranolol concentration, whereas the expression of nuclear factor-κBp65, phosphorylated inhibitor of κB alpha (p-IκBα), and phosphorylated inhibitor of nuclear factor-κB kinase beta (p-IκKβ) weakened gradually (p < 0.05). In vivo, the tumors shrank gradually after propranolol treatment, with an increase in thrombospondin-1 and CD36 and a decrease in nuclear factor-κBp65, p-IκBα, and p-IκKβ (p < 0.05). Glucocorticoid improved the antiangiogenesis mediated by thrombospondin-1/CD36 and inhibited the angiogenesis mediated by nuclear factor-κB/IκB (p < 0.05). Negative regulation occurred between the two signaling pathways.
The treatment of infantile hemangioma with propranolol is promising to promote thrombospondin-1-mediated antiangiogenesis and to block nuclear factor-κB-mediated angiogenesis. |
| doi_str_mv | 10.1097/PRS.0000000000004684 |
| format | Article |
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The hemangioma-derived endothelial cells were sorted out from the specimens of proliferative hemangioma by flow cytometry. Furthermore, a BALB/c nude mouse hemangioma model was established. Viability and proliferation of hemangioma-derived endothelial cells and the role of thrombospondin-1 and nuclear factor-κB signaling pathways were observed after propranolol administration in vitro and in vivo.
The expression of thrombospondin-1 and its receptor CD36 in hemangioma-derived endothelial cells gradually increased with the increase in propranolol concentration, whereas the expression of nuclear factor-κBp65, phosphorylated inhibitor of κB alpha (p-IκBα), and phosphorylated inhibitor of nuclear factor-κB kinase beta (p-IκKβ) weakened gradually (p < 0.05). In vivo, the tumors shrank gradually after propranolol treatment, with an increase in thrombospondin-1 and CD36 and a decrease in nuclear factor-κBp65, p-IκBα, and p-IκKβ (p < 0.05). Glucocorticoid improved the antiangiogenesis mediated by thrombospondin-1/CD36 and inhibited the angiogenesis mediated by nuclear factor-κB/IκB (p < 0.05). Negative regulation occurred between the two signaling pathways.
The treatment of infantile hemangioma with propranolol is promising to promote thrombospondin-1-mediated antiangiogenesis and to block nuclear factor-κB-mediated angiogenesis.</description><identifier>ISSN: 0032-1052</identifier><identifier>EISSN: 1529-4242</identifier><identifier>DOI: 10.1097/PRS.0000000000004684</identifier><identifier>PMID: 30148773</identifier><language>eng</language><publisher>United States: by the American Society of Plastic Surgeons</publisher><subject>Adrenergic beta-Antagonists - pharmacology ; Adrenergic beta-Antagonists - therapeutic use ; Animals ; Cell Proliferation - drug effects ; Endothelial Cells - drug effects ; Female ; Hemangioma - drug therapy ; Hemangioma - pathology ; Humans ; I-kappa B Proteins - metabolism ; Infant ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neovascularization, Pathologic - drug therapy ; Neovascularization, Pathologic - pathology ; NF-KappaB Inhibitor alpha - metabolism ; Propranolol - pharmacology ; Propranolol - therapeutic use ; Signal Transduction - drug effects ; Skin Neoplasms - drug therapy ; Skin Neoplasms - pathology ; Thrombospondin 1 - metabolism ; Transcription Factor RelA - metabolism ; Treatment Outcome ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays</subject><ispartof>Plastic and reconstructive surgery (1963), 2018-09, Vol.142 (3), p.310e-321e</ispartof><rights>by the American Society of Plastic Surgeons</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3193-3c445b5721f859e3eab2b1464956aebd99ed1c77c6aab97f2fdff657cc1475ad3</citedby><cites>FETCH-LOGICAL-c3193-3c445b5721f859e3eab2b1464956aebd99ed1c77c6aab97f2fdff657cc1475ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30148773$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Weili</creatorcontrib><creatorcontrib>Li, Suolin</creatorcontrib><creatorcontrib>Yu, Fengxue</creatorcontrib><creatorcontrib>Zhang, Yongting</creatorcontrib><creatorcontrib>Yang, Xiaofeng</creatorcontrib><creatorcontrib>An, Wenting</creatorcontrib><creatorcontrib>Wang, Wenbo</creatorcontrib><creatorcontrib>Sun, Chi</creatorcontrib><title>Role of Thrombospondin-1 and Nuclear Factor-κB Signaling Pathways in Antiangiogenesis of Infantile Hemangioma</title><title>Plastic and reconstructive surgery (1963)</title><addtitle>Plast Reconstr Surg</addtitle><description>Propranolol is the first-line drug for treatment of infantile hemangioma. However, its mechanism of action remains unclear. Nuclear factor-κB is highly expressed in tumors, directly or indirectly promoting angiogenesis. Thrombospondin-1 is the most important antiangiogenesis protein in vivo. These proteins mediate signaling pathways, probably playing an important role in hemangioma treatment. This study explored the synergistic regulation of thrombospondin-1 and nuclear factor-κB signaling pathways in the treatment of hemangioma with propranolol.
The hemangioma-derived endothelial cells were sorted out from the specimens of proliferative hemangioma by flow cytometry. Furthermore, a BALB/c nude mouse hemangioma model was established. Viability and proliferation of hemangioma-derived endothelial cells and the role of thrombospondin-1 and nuclear factor-κB signaling pathways were observed after propranolol administration in vitro and in vivo.
The expression of thrombospondin-1 and its receptor CD36 in hemangioma-derived endothelial cells gradually increased with the increase in propranolol concentration, whereas the expression of nuclear factor-κBp65, phosphorylated inhibitor of κB alpha (p-IκBα), and phosphorylated inhibitor of nuclear factor-κB kinase beta (p-IκKβ) weakened gradually (p < 0.05). In vivo, the tumors shrank gradually after propranolol treatment, with an increase in thrombospondin-1 and CD36 and a decrease in nuclear factor-κBp65, p-IκBα, and p-IκKβ (p < 0.05). Glucocorticoid improved the antiangiogenesis mediated by thrombospondin-1/CD36 and inhibited the angiogenesis mediated by nuclear factor-κB/IκB (p < 0.05). Negative regulation occurred between the two signaling pathways.
The treatment of infantile hemangioma with propranolol is promising to promote thrombospondin-1-mediated antiangiogenesis and to block nuclear factor-κB-mediated angiogenesis.</description><subject>Adrenergic beta-Antagonists - pharmacology</subject><subject>Adrenergic beta-Antagonists - therapeutic use</subject><subject>Animals</subject><subject>Cell Proliferation - drug effects</subject><subject>Endothelial Cells - drug effects</subject><subject>Female</subject><subject>Hemangioma - drug therapy</subject><subject>Hemangioma - pathology</subject><subject>Humans</subject><subject>I-kappa B Proteins - metabolism</subject><subject>Infant</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>NF-KappaB Inhibitor alpha - metabolism</subject><subject>Propranolol - pharmacology</subject><subject>Propranolol - therapeutic use</subject><subject>Signal Transduction - drug effects</subject><subject>Skin Neoplasms - drug therapy</subject><subject>Skin Neoplasms - pathology</subject><subject>Thrombospondin 1 - metabolism</subject><subject>Transcription Factor RelA - metabolism</subject><subject>Treatment Outcome</subject><subject>Tumor Cells, Cultured</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0032-1052</issn><issn>1529-4242</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkFlKBDEQhoMoOi43EMkFolk7k8dxcANRcXluqtPJTGt3MiQ9DF7NQ3gm210sKIqq4v8ePoT2GT1k1Oijm9u7Q_qnZDGWa2jEFDdEcsnX0YhSwQmjim-h7ZwfKWVaFGoTbQnK5FhrMULhNrYOR4_v5yl2VcyLGOomEIYh1PhqaVsHCZ-C7WMiry_H-K6ZBWibMMM30M9X8JxxE_Ak9A2EWRNnLrjc5HfiRfAwnAf8ues-nh3sog0PbXZ7X3MHPZye3E_PyeX12cV0ckmsYEYQYaVUldKc-bEyTjioeMVkIY0qwFW1Ma5mVmtbAFRGe-5r7wulrWVSK6jFDpKfXJtizsn5cpGaDtJzyWj5rq8c9JX_9Q2xg8_YYll1rv4Jffv65a5i27uUn9rlyqVy7qDt5x-8QglJOGVjaoaNDM2FeAMddny-</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>Xu, Weili</creator><creator>Li, Suolin</creator><creator>Yu, Fengxue</creator><creator>Zhang, Yongting</creator><creator>Yang, Xiaofeng</creator><creator>An, Wenting</creator><creator>Wang, Wenbo</creator><creator>Sun, Chi</creator><general>by the American Society of Plastic Surgeons</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20180901</creationdate><title>Role of Thrombospondin-1 and Nuclear Factor-κB Signaling Pathways in Antiangiogenesis of Infantile Hemangioma</title><author>Xu, Weili ; Li, Suolin ; Yu, Fengxue ; Zhang, Yongting ; Yang, Xiaofeng ; An, Wenting ; Wang, Wenbo ; Sun, Chi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3193-3c445b5721f859e3eab2b1464956aebd99ed1c77c6aab97f2fdff657cc1475ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adrenergic beta-Antagonists - pharmacology</topic><topic>Adrenergic beta-Antagonists - therapeutic use</topic><topic>Animals</topic><topic>Cell Proliferation - drug effects</topic><topic>Endothelial Cells - drug effects</topic><topic>Female</topic><topic>Hemangioma - drug therapy</topic><topic>Hemangioma - pathology</topic><topic>Humans</topic><topic>I-kappa B Proteins - metabolism</topic><topic>Infant</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>NF-KappaB Inhibitor alpha - metabolism</topic><topic>Propranolol - pharmacology</topic><topic>Propranolol - therapeutic use</topic><topic>Signal Transduction - drug effects</topic><topic>Skin Neoplasms - drug therapy</topic><topic>Skin Neoplasms - pathology</topic><topic>Thrombospondin 1 - metabolism</topic><topic>Transcription Factor RelA - metabolism</topic><topic>Treatment Outcome</topic><topic>Tumor Cells, Cultured</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Weili</creatorcontrib><creatorcontrib>Li, Suolin</creatorcontrib><creatorcontrib>Yu, Fengxue</creatorcontrib><creatorcontrib>Zhang, Yongting</creatorcontrib><creatorcontrib>Yang, Xiaofeng</creatorcontrib><creatorcontrib>An, Wenting</creatorcontrib><creatorcontrib>Wang, Wenbo</creatorcontrib><creatorcontrib>Sun, Chi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Plastic and reconstructive surgery (1963)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Weili</au><au>Li, Suolin</au><au>Yu, Fengxue</au><au>Zhang, Yongting</au><au>Yang, Xiaofeng</au><au>An, Wenting</au><au>Wang, Wenbo</au><au>Sun, Chi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of Thrombospondin-1 and Nuclear Factor-κB Signaling Pathways in Antiangiogenesis of Infantile Hemangioma</atitle><jtitle>Plastic and reconstructive surgery (1963)</jtitle><addtitle>Plast Reconstr Surg</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>142</volume><issue>3</issue><spage>310e</spage><epage>321e</epage><pages>310e-321e</pages><issn>0032-1052</issn><eissn>1529-4242</eissn><abstract>Propranolol is the first-line drug for treatment of infantile hemangioma. However, its mechanism of action remains unclear. Nuclear factor-κB is highly expressed in tumors, directly or indirectly promoting angiogenesis. Thrombospondin-1 is the most important antiangiogenesis protein in vivo. These proteins mediate signaling pathways, probably playing an important role in hemangioma treatment. This study explored the synergistic regulation of thrombospondin-1 and nuclear factor-κB signaling pathways in the treatment of hemangioma with propranolol.
The hemangioma-derived endothelial cells were sorted out from the specimens of proliferative hemangioma by flow cytometry. Furthermore, a BALB/c nude mouse hemangioma model was established. Viability and proliferation of hemangioma-derived endothelial cells and the role of thrombospondin-1 and nuclear factor-κB signaling pathways were observed after propranolol administration in vitro and in vivo.
The expression of thrombospondin-1 and its receptor CD36 in hemangioma-derived endothelial cells gradually increased with the increase in propranolol concentration, whereas the expression of nuclear factor-κBp65, phosphorylated inhibitor of κB alpha (p-IκBα), and phosphorylated inhibitor of nuclear factor-κB kinase beta (p-IκKβ) weakened gradually (p < 0.05). In vivo, the tumors shrank gradually after propranolol treatment, with an increase in thrombospondin-1 and CD36 and a decrease in nuclear factor-κBp65, p-IκBα, and p-IκKβ (p < 0.05). Glucocorticoid improved the antiangiogenesis mediated by thrombospondin-1/CD36 and inhibited the angiogenesis mediated by nuclear factor-κB/IκB (p < 0.05). Negative regulation occurred between the two signaling pathways.
The treatment of infantile hemangioma with propranolol is promising to promote thrombospondin-1-mediated antiangiogenesis and to block nuclear factor-κB-mediated angiogenesis.</abstract><cop>United States</cop><pub>by the American Society of Plastic Surgeons</pub><pmid>30148773</pmid><doi>10.1097/PRS.0000000000004684</doi></addata></record> |
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| ispartof | Plastic and reconstructive surgery (1963), 2018-09, Vol.142 (3), p.310e-321e |
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| source | MEDLINE; Journals@Ovid Complete - AutoHoldings |
| subjects | Adrenergic beta-Antagonists - pharmacology Adrenergic beta-Antagonists - therapeutic use Animals Cell Proliferation - drug effects Endothelial Cells - drug effects Female Hemangioma - drug therapy Hemangioma - pathology Humans I-kappa B Proteins - metabolism Infant Mice Mice, Inbred BALB C Mice, Nude Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - pathology NF-KappaB Inhibitor alpha - metabolism Propranolol - pharmacology Propranolol - therapeutic use Signal Transduction - drug effects Skin Neoplasms - drug therapy Skin Neoplasms - pathology Thrombospondin 1 - metabolism Transcription Factor RelA - metabolism Treatment Outcome Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| title | Role of Thrombospondin-1 and Nuclear Factor-κB Signaling Pathways in Antiangiogenesis of Infantile Hemangioma |
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