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. (C) 1995 Wiley-Liss, Inc.