title: Upregulated periostin promotes angiogenesis in keloids through activation of the ERK 1/2 and focal adhesion kinase pathways, as well as the upregulated expression of VEGF and angiopoietin‑1.
abstract: Periostin, a secreted extracellular matrix protein, is highly expressed in wound healing and in various types of human cancer and is involved in angiogenesis. Keloids, considered dermal benign tumors, are granulomatous lesions characterized by capillary proliferation. However, the underlying regulatory mechanism of angiogenesis in keloids remains to be elucidated. The present study aimed to examine the effect of periostin on angiogenesis in keloids. The expression of periostin was upregulated and the vessel density was higher in human keloids compared with normal tissue, observed following staining with CD31 and CD105. Periostin demonstrated a markedly positive correlation with blood vessel density, which was assessed using CD31 staining (r=0.711; P<0.01) and a weak correlation was observed using CD105 staining (r=0.251; P<0.01). Conditioned medium from keloid fibroblasts (KFs) promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) compared with normal fibroblasts and this effect may have been abrogated by the short hairpin RNA knockdown of periostin. Treatment with recombinant human periostin promoted the migration and tube formation of HUVECs by activating the extracellular signal‑regulated kinase 1/2 and focal adhesion kinase signaling pathway. In addition, periostin increased the secretion of vascular endothelial growth factor and angiopoietin‑1 in the KFs. In conclusion, these data suggested that upregulation in the level of periostin may promote angiogenesis directly and indirectly in keloids and may be a key factor in keloid development. Periostin may, therefore, be a promising therapeutic target in the treatment of keloids and other angioproliferative diseases.
authors.affiliation: Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Fangfei
authors.initials: F
authors.lastname: Nie
authors.affiliation: Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Zelian
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Kang
authors.affiliation: Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Bolin
authors.initials: B
authors.lastname: Pan
authors.affiliation: Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China.
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007627:Keloid / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D055815:Young Adult
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D042461:Vascular Endothelial Growth Factor A; D051417:Focal Adhesion Kinase 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3