title: Fibromodulin promoted in vitro and in vivo angiogenesis.
abstract: Fibromodulin (FMOD) is an extracellular matrix (ECM) small leucine-rich proteoglycan (SLRP) that plays an important role in cell fate determination. Previous studies revealed that not only is FMOD critical in fetal-type scarless wound healing, but it also promotes adult wound closure and reduces scar formation. In addition, FMOD-deficient mice exhibit significantly reduced blood vessel regeneration in granulation tissues during wound healing. In this study, we investigated the effects of FMOD on angiogenesis, which is an important event in wound healing as well as embryonic development and tumorigenesis. We found that FMOD accelerated human umbilical vein endothelial HUVEC-CS cell adhesion, spreading, actin stress fiber formation, and eventually tube-like structure (TLS) network establishment in vitro. On a molecular level, by increasing expression of collagen I and III, angiopoietin (Ang)-2, and vascular endothelial growth factor (VEGF), as well as reducing the ratio of Ang-1/Ang-2, FMOD provided a favorable network to mobilize quiescent endothelial cells to an angiogenic phenotype. Moreover, we also confirmed that FMOD enhanced angiogenesis in vivo by using an in ovo chick embryo chorioallantoic membrane (CAM) assay. Therefore, our data demonstrate that FMOD is a pro-angiogenic and suggest a potential therapeutic role of FMOD in the treatment of conditions related to impaired angiogenesis.
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Jian
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Kermit
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Todd Matthew
authors.initials: TM
authors.lastname: Rackohn
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Chingyun
authors.initials: C
authors.lastname: Hsu
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Levin
authors.affiliation: Department of Psychobiology, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Dwarak Reddy
authors.initials: DR
authors.lastname: Enjamuri
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery and Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects; D024061:Collagen Type III / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D000071235:Fibromodulin; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011509:Proteoglycans / Q000494:pharmacology*; D022502:Stress Fibers / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D042702:Angiopoietin-2; D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C000604332:Fmod protein, mouse; D011509:Proteoglycans; C488955:VCL protein, human; D016596:Vinculin; D000071235:Fibromodulin
keywords: Angiogenesis; Fibromodulin; Human endothelial HUVEC-CS cell; In ovo chick embryo chorioallantoic membrane (CAM) assay; Tube-like structure formation