Proteoglycan biosynthesis is required in BC3H1 myogenic cells for modulation of vascular smooth muscle alpha-actin gene expression in response to microenvironmental signals.
Induction of vascular smooth muscle (VSM) alpha-actin mRNA expression during cytodifferentiation of mouse BC3H1 myogenic cells coincides with the accumulation of cell surface- and extracellular matrix-associated sulfated proteoglycans. Inhibition of proteoglycan biosynthesis in myogenic cells using an artificial beta-D-xyloside glycosaminoglycan acceptor was accompanied by a reduction in cell surface/extracellular matrix proteoglycans and VSM alpha-actin mRNA expression while enhancing the secretion of free chondroitin sulfate/dermatan sulfate and heparan sulfate glycosaminoglycans into the culture medium. Maximum inhibition of VSM alpha-actin mRNA expression required that proteoglycan biosynthesis be blocked during the early phase of cytodifferentiation when myoblasts were fully confluent and quiescent. The inhibitory effect of beta-D-xyloside on alpha-actin mRNA expression resulted from attenuation at both the transcriptional and post-transcriptional control points. Sustained proteoglycan biosynthesis was required for induction of VSM alpha-actin mRNA in quiescent myoblasts in response to cytodifferentiation-permissive, substrate-associated macromolecules (SAM) or upon exposure to soluble serum factors capable of transiently stimulating VSM alpha-actin gene transcription. The results suggested that efficient myoblast cytodifferentiation and modulation of VSM alpha-actin mRNA levels depended on intact cell surface proteoglycans to convey signals generated as a consequence of cellular interaction with substrate components and serum factors.
Lee
S H
SH
Department of Cell Biology, College of Medicine, Ohio State University, Columbus 43210, USA.
Yan
H
H
Reeser
J C
JC
Dillman
J M
JM
Strauch
A R
AR
D000199:Actins / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation; D006025:Glycosaminoglycans / Q000494:pharmacology; D006027:Glycosides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D053667:Syndecans; D014158:Transcription, Genetic / Q000187:drug effects
D000199:Actins; D006025:Glycosaminoglycans; D006027:Glycosides; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D053667:Syndecans; C010807:xylosides