{"title":"TGF-β1 Promotes Angiogenesis via Endothelial-to-Mesenchymal Transition in Infantile Hemangioma.","authors":"Xue Gong, Tong Qiu, Jiangyuan Zhou, Kaiying Yang, Shanshan Xiang, Zixin Zhang, Yuru Lan, Xuepeng Zhang, Zilong Zhou, Congxia Yang, Yujia Zhang, Siyuan Chen, Yi Ji","doi":"10.1161/ATVBAHA.125.322793","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Infantile hemangioma (IH) is the most common benign tumor in infancy and severely affects aesthetics and function. Hemangioma-derived endothelial cells (HemECs) are the main cellular component of IH and contribute to angiogenesis in IH. TGF-β1 (transforming growth factor β1) can induce endothelial-to-mesenchymal transition (EndoMT). Few studies have investigated the role and mechanism of TGF-β1-mediated EndoMT in IH angiogenesis.</p><p><strong>Methods: </strong>The expression of EndoMT markers in IH samples was evaluated via multiplexed immunofluorescence assay. Lentiviruses and small interfering RNA were used to regulate gene expression. Targeted lipidomic analysis was subsequently conducted. Protein interactions between TGF-β1 and potential effectors were examined. Biological changes in function were measured by migration, invasion, and tube formation in vitro and vessel formation in vivo. Autophagy-related structures were detected via transmission electron microscopy. BALB/C-nude mice were used for the hemangioma model.</p><p><strong>Results: </strong>In this study, the active participation of EndoMT in proliferating IH was verified. TGF-β1<sup>OE</sup> (TGF-β1 overexpression) induced EndoMT and promoted the migration, invasion, and angiogenic abilities of HemECs. In addition, TGF-β1<sup>OE</sup> decreased the protein expression of CPT1A (carnitine palmitoyltransferase 1A). TGF-β1 treatment decreased the levels of L-palmitoylcarnitine (a downstream metabolite of CPT1A) in HemECs. Supplementation with L-palmitoylcarnitine partly reversed the functional changes caused by CPT1A<sup>KD</sup> (CPT1A knockdown). Furthermore, the effect of TGF-β1<sup>OE</sup>+overexpression model of CPT1A was similar to that of CPT1A<sup>KD</sup>+L-palmitoylcarnitine in regulating the functional behaviors of HemECs. R(+) propranolol inhibited HemECs EndoMT and vessel formation in vivo.</p><p><strong>Conclusions: </strong>TGF-β1-mediated EndoMT promotes angiogenesis in IH. Targeting TGF-β1 could be a promising therapeutic strategy for inhibiting IH progression.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1912-1927"},"PeriodicalIF":7.4000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453102/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arteriosclerosis, Thrombosis, and Vascular Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/ATVBAHA.125.322793","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/21 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Infantile hemangioma (IH) is the most common benign tumor in infancy and severely affects aesthetics and function. Hemangioma-derived endothelial cells (HemECs) are the main cellular component of IH and contribute to angiogenesis in IH. TGF-β1 (transforming growth factor β1) can induce endothelial-to-mesenchymal transition (EndoMT). Few studies have investigated the role and mechanism of TGF-β1-mediated EndoMT in IH angiogenesis.
Methods: The expression of EndoMT markers in IH samples was evaluated via multiplexed immunofluorescence assay. Lentiviruses and small interfering RNA were used to regulate gene expression. Targeted lipidomic analysis was subsequently conducted. Protein interactions between TGF-β1 and potential effectors were examined. Biological changes in function were measured by migration, invasion, and tube formation in vitro and vessel formation in vivo. Autophagy-related structures were detected via transmission electron microscopy. BALB/C-nude mice were used for the hemangioma model.
Results: In this study, the active participation of EndoMT in proliferating IH was verified. TGF-β1OE (TGF-β1 overexpression) induced EndoMT and promoted the migration, invasion, and angiogenic abilities of HemECs. In addition, TGF-β1OE decreased the protein expression of CPT1A (carnitine palmitoyltransferase 1A). TGF-β1 treatment decreased the levels of L-palmitoylcarnitine (a downstream metabolite of CPT1A) in HemECs. Supplementation with L-palmitoylcarnitine partly reversed the functional changes caused by CPT1AKD (CPT1A knockdown). Furthermore, the effect of TGF-β1OE+overexpression model of CPT1A was similar to that of CPT1AKD+L-palmitoylcarnitine in regulating the functional behaviors of HemECs. R(+) propranolol inhibited HemECs EndoMT and vessel formation in vivo.
Conclusions: TGF-β1-mediated EndoMT promotes angiogenesis in IH. Targeting TGF-β1 could be a promising therapeutic strategy for inhibiting IH progression.
期刊介绍：
The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA).
The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
