Overexpression of decorin by rat arterial smooth muscle cells enhances contraction of type I collagen in vitro.
OBJECTIVE
Overexpression of decorin reduces neointimal thickening in balloon-injured carotid arteries of rats by decreasing the volume of neointimal extracellular matrix (ECM). We examined the hypothesis that decorin regulates ECM volume by stimulating cell-mediated contraction of collagen-rich ECMs.


RESULTS
Rat arterial smooth muscle cells (ASMCs) transduced with bovine decorin cDNA by retroviral transfection (LDSN) exhibited enhanced contraction of collagen gels in vitro when compared with vector-only transduced (LXSN) cells. Addition of recombinant decorin to LXSN or LDSN cells did not stimulate contraction of collagen gels. Enhanced contraction of collagen by LDSN cells was unaffected by the metalloproteinase inhibitor GM6001. LDSN cells exhibited increased expression of type I collagen mRNA when compared with that of LXSN cells. Correspondingly, collagen gel contraction by LDSN cells was reduced by inhibition of collagen synthesis by 3,4-l-dehydroproline (L-DHP). Antibodies to alpha1beta1-integrin, but not to alpha2beta1-integrin, blocked collagen contraction by both LXSN and LDSN cells. However, LXSN and LDSN cells expressed similar levels of alpha1- and beta1-integrin mRNAs.


CONCLUSIONS
Decorin synthesized de novo by ASMCs increases type I collagen synthesis and enhances contraction of collagen gels. Regulated synthesis of decorin may be a useful therapeutic approach to reduce ECM volume in vascular disease.
Järveläinen
Hannu
H
Department of Medicine, University of Turku, Finland.
Vernon
Robert B
RB
Gooden
Michel D
MD
Francki
Aleksandar
A
Lara
Stephanie
S
Johnson
Pamela Y
PY
Kinsella
Michael G
MG
Sage
E Helene
EH
Wight
Thomas N
TN
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D058575:Decorin; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005782:Gels; D006801:Humans; D066298:In Vitro Techniques; D039222:Integrin alpha1beta1 / Q000037:antagonists & inhibitors / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000502:physiology; D014161:Transduction, Genetic
C546878:DCN protein, human; D018076:DNA, Complementary; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005782:Gels; D039222:Integrin alpha1beta1; D011509:Proteoglycans; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C002195:3,4-dehydroproline; D003094:Collagen; D011392:Proline