title: Matricellular hevin regulates decorin production and collagen assembly.
abstract: Matricellular proteins such as SPARC, thrombospondin 1 and 2, and tenascin C and X subserve important functions in extracellular matrix synthesis and cellular adhesion to extracellular matrix. By virtue of its reported interaction with collagen I and deadhesive activity on cells, we hypothesized that hevin, a member of the SPARC gene family, regulates dermal extracellular matrix and collagen fibril formation. We present evidence for an altered collagen matrix and levels of the proteoglycan decorin in the normal dermis and dermal wound bed of hevin-null mice. The dermal elastic modulus was also enhanced in hevin-null animals. The levels of decorin protein secreted by hevin-null dermal fibroblasts were increased by exogenous hevin in vitro, data indicating that hevin might regulate both decorin and collagen fibrillogenesis. We also report a decorin-independent function for hevin in collagen fibrillogenesis. In vitro fibrillogenesis assays indicated that hevin enhanced fibril formation kinetics. Furthermore, cell adhesion assays indicated that cells adhered differently to collagen fibrils formed in the presence of hevin. Our observations support the capacity of hevin to modulate the structure of dermal extracellular matrix, specifically by its regulation of decorin levels and collagen fibril assembly.
authors.affiliation: Hope Heart Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101, USA.
authors.forename: Millicent M
authors.initials: MM
authors.lastname: Sullivan
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Barker
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Funk
authors.forename: Ari
authors.initials: A
authors.lastname: Karchin
authors.forename: Neung S
authors.initials: NS
authors.lastname: Seo
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
authors.forename: Joan
authors.initials: J
authors.lastname: Sanders
authors.forename: Barry
authors.initials: B
authors.lastname: Starcher
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
authors.forename: Pauli
authors.initials: P
authors.lastname: Puolakkainen
authors.forename: E Helene
authors.initials: EH
authors.lastname: Sage
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D002448:Cell Adhesion; D003094:Collagen / Q000737:chemistry*; D058575:Decorin; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D051379:Mice; D011509:Proteoglycans / Q000737:chemistry*; D012867:Skin / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; C503126:SPARCL1 protein, human; C503127:Sparcl1 protein, mouse; D003094:Collagen