Matricellular hevin regulates decorin production and collagen assembly.
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.
Sullivan
Millicent M
MM
Hope Heart Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101, USA.
Barker
Thomas H
TH
Funk
Sarah E
SE
Karchin
Ari
A
Seo
Neung S
NS
Höök
Magnus
M
Sanders
Joan
J
Starcher
Barry
B
Wight
Thomas N
TN
Puolakkainen
Pauli
P
Sage
E Helene
EH
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
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