Regulation of vascular smooth muscle cell proliferation, migration and death by heparan sulfate 6-O-endosulfatase1.
Migration, proliferation and death of vascular smooth muscle cells (VSMC) are important events in vascular pathology regulated by heparan sulfate proteoglycans and hence potentially by cell surface HS 6-O-endosulfatase1 (sulf1). Sulf1 mRNA expression was increased in cultured VSMC compared to rat aorta. Furthermore, adenovirus mediated overexpression of quail sulf1 decreased adhesion, and increased proliferation and apoptosis of VSMC. Overexpression of a dominant negative variant also decreased adhesion of VSMC and increased proliferation, apoptosis, migration and chemotaxis of VSMC. Our results imply that only normal levels of 6-O-sulfation maintained by sulf1 are optimal for several functions of VSMC.
Sala-Newby
Graciela B
GB
Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom. g.newby@bristol.ac.uk
George
Sarah J
SJ
Bond
Mark
M
Dhoot
Gurtej K
GK
Newby
Andrew C
AC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000201:enzymology; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D009154:Mutation / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D013429:Sulfatases / Q000235:genetics / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C470791:SULF1 protein, human; D015238:Sulfotransferases; C477242:QSulf1; D013429:Sulfatases