TGF-β1 Promotes Angiogenesis via Endothelial-to-Mesenchymal Transition in Infantile Hemangioma

作者：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 · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2025 · DOI：10.1161/atvbaha.125.322793 · 被引用次数：10 · 研究领域：Vascular Malformations and Hemangiomas、Vascular Tumors and Angiosarcomas、Cancer, Hypoxia, and Metabolism

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-β1 OE (TGF-β1 overexpression) induced EndoMT and promoted the migration, invasion, and angiogenic abilities of HemECs. In addition, TGF-β1 OE 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 part...