Balloon catheterization induces arterial expression of new Tenascin-C isoform.
Migration of smooth muscle cells (SMCs) across the internal elastic lamina is a key step in the development of atherosclerotic or restenotic plaques. Cell movement is a complex and highly dynamic phenomenon, involving the continuous formation and breakage of attachments with the underlying substratum. Tenascin-C (Tn-C), a counter-adhesive extracellular matrix protein, is comprised of several isoforms with distinct biological activities. Neither the structure nor function of these isoforms in SMCs has been defined. We have used primers and RT-PCR to fully identify Tn-C isoforms expressed by SMCs. Cloning and sequence analysis of the PCR product indicated that SMCs express a Tn-C isoform with only repeats A1 and A2 of fibronectin type III repeats. Using A1A2-specific antibodies, cDNA probes and RNase mapping, we observed that the A1A2 isoform is predominantly expressed by cultured SMCs derived from aorta of newborn rats, and its expression is up-regulated by PDGF-BB. In contrast, the expression of this isoform is markedly down-regulated in the SMCs derived from adult rat aorta. Western and Northern blots of injured rat carotid arteries revealed that the A1A2-isoform is expressed in response to injury. Using cultured SMCs, we found that the recombinant A1A2 protein that was found in the newly discovered Tn-C isoform promotes SMC chemotaxis. We conclude that Tn-C isoforms are expressed in a regulated fashion in vascular system. Our findings suggest a new role of Tn-C isoforms in the remodeling of vascular wall.
Wallner
Kurt
K
Atherosclerosis Research Center, Division of Cardiology, Burns and Allen Research Institute, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Shah
Prediman K
PK
Sharifi
Behrooz G
BG
D000818:Animals; D000077214:Becaplermin; D015153:Blotting, Western; D002404:Catheterization; D002465:Cell Movement; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011487:Protein Conformation; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism; D019063:Tenascin / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D019063:Tenascin; D000077214:Becaplermin; D012260:Ribonucleases