title: Effect of adenoviral mediated overexpression of fibromodulin on human dermal fibroblasts and scar formation in full-thickness incisional wounds.
abstract: Fibromodulin, a member of the small leucine-rich proteoglycan family, has been recently suggested as a biologically significant mediator of fetal scarless repair. To assess the role of fibromodulin in the tissue remodeling, we constructed an adenoviral vector expressing human fibromodulin cDNA. We evaluated the effect of adenovirus-mediated overexpression of fibromodulin in vitro on transforming growth factors and metalloproteinases in fibroblasts and in vivo on full-thickness incisional wounds in a rabbit model. In vitro, we found that Ad-Fibromodulin induced a decrease of expression of TGF-beta(1) and TGF-beta(2) precursor proteins, but an increase in expression of TGF-beta(3) precursor protein and TGF-beta type II receptor. In addition, fibromodulin overexpression resulted in decreased MMP-1 and MMP-3 protein secretion but increased MMP-2, TIMP-1, and TIMP-2 secretion, whereas MMP-9 and MMP-13 were not influenced by fibromodulin overexpression. In vivo evaluation by histopathology and tensile strength demonstrated that Ad-Fibromodulin administration could ameliorate wound healing in incisional wounds. In conclusion, although the mechanism of scar formation in adult wounds remains incompletely understood, we found that fibromodulin overexpression improves wound healing in vivo, suggesting that fibromodulin may be a key mediator in reduced scarring.
authors.affiliation: Division of Human Gene Therapy, Gene Therapy Center, University of Alabama at Birmingham, 901 19th Street South, BMR2 502, Birmingham, AL, 35294-2172, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stoff
authors.forename: Angel A
authors.initials: AA
authors.lastname: Rivera
authors.forename: J Michael
authors.initials: JM
authors.lastname: Mathis
authors.forename: Steven T
authors.initials: ST
authors.lastname: Moore
authors.forename: N S
authors.initials: NS
authors.lastname: Banerjee
authors.forename: Maaike
authors.initials: M
authors.lastname: Everts
authors.forename: Antonio
authors.initials: A
authors.lastname: Espinosa-de-los-Monteros
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Novak
authors.forename: Luis O
authors.initials: LO
authors.lastname: Vasconez
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Broker
authors.forename: Dirk F
authors.initials: DF
authors.lastname: Richter
authors.forename: Dale
authors.initials: D
authors.lastname: Feldman
authors.forename: Gene P
authors.initials: GP
authors.lastname: Siegal
authors.forename: Mariam A
authors.initials: MA
authors.lastname: Stoff-Khalili
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D062109:Dermatologic Surgical Procedures; D020405:Dermis / Q000166:cytology / Q000378:metabolism*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism*; D000071235:Fibromodulin; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D011817:Rabbits; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D013718:Tensile Strength; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014162:Transfection; D015291:Transforming Growth Factors / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
chemical_list: D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D019714:Tissue Inhibitor of Metalloproteinases; D000071235:Fibromodulin; D015291:Transforming Growth Factors; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D053505:Matrix Metalloproteinases, Secreted