title: Role of pigment epithelium-derived factor in the involution of hemangioma: autocrine growth inhibition of hemangioma-derived endothelial cells.
abstract: Hemangioma is a benign tumor derived from abnormal blood vessel growth. Unlike other vascular tumor counterparts, a hemangioma is known to proliferate during its early stage but it is followed by a stage of involution where regression of the tumor occurs. The critical onset leading to the involution of hemangioma is currently not well understood. This study focused on the molecular identities of the involution of hemangioma. We demonstrated that a soluble factor released from the involuting phase of hemangioma-derived endothelial cells (HemECs) and identified pigment epithelium-derived factor (PEDF) as an anti-angiogenic factor that was associated with the growth inhibition of the involuting HemECs. The growth inhibition of the involuting HemECs was reversed by suppression of PEDF in the involuting HemECs. Furthermore, we found that PEDF was more up-regulated in the involuting phase of hemangioma tissues than in the proliferating or the involuted. Taken together, we propose that PEDF accelerates the involution of hemangioma by growth inhibition of HemECs in an autocrine manner. The regulatory mechanism of PEDF expression could be a potential therapeutic target to treat hemangiomas.
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea; Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Jang-Hyuk
authors.initials: JH
authors.lastname: Yun
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Jong-Ik
authors.initials: JI
authors.lastname: Heo
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.affiliation: Department of Plastic and Reconstructive Surgery, Seoul National University Children's Hospital, Seoul 110-744, Republic of Korea; Department of Pediatric Plastic and Reconstructive Surgery, Seoul National University Children's Hospital, Seoul 110-744, Republic of Korea. Electronic address: psthchoi@snu.ac.kr.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea; Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea; Ischemic/Hypoxic Disease Institute, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea; Cancer Research Institute, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea. Electronic address: iamhyun@snu.ac.kr.
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
mesh_terms: D017209:Apoptosis; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006391:Hemangioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009389:Neovascularization, Pathologic; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D034741:RNA, Small Interfering; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor
keywords: Angiogenesis; Endothelial cell; Hemangioma; Involution; Pigment epithelium-derived factor