Laminin variants and integrin laminin receptors in developing and adult human smooth muscle.
Distribution of laminin variant chains and of laminin-binding beta 1-associated alpha integrin subunits was studied in human arterial and visceral smooth muscle during development using the immunofluorescence method. In aortic media of 10-week-old fetuses (early fetal stage of development), B1, B2, and A chains were found, and at 27 weeks of gestation (late fetal step), in addition, the S chain was revealed. In the major part of adult aortic media, staining for the B1 chain was substituted by staining for the S chain. A reasonable explanation for this is that the basement membrane of arterial SMCs contains the A-B1-B2 laminin trimer at the early fetal stage of development, a mixture of A-B1-B2 and A-S-B2 variants during the late fetal period, and the A-S-B2 form in adult media. In the intimal thickening of adult arteries, staining for A and S chains was decreased, and the B1 chain was detected, thus suggesting coexistence of A-B1-B2 and A-S-B2 variants similar to the fetal aorta. These data led us to propose that maturation of arterial SMCs is accompanied by a switch from expression of A-B1-B2 to A-S-B2 laminin, the only protein variant associated with the differentiated SMC phenotype. The M chain was not detected in fetal and adult arterial smooth muscle. In differentiated visceral SMCs from adult colon, in contrast to arterial medial SMCs, B1, S, B2, and A chains, i.e., both B1 chain- and S chain-containing laminin molecules, were present. Similar to vascular smooth muscle, the expression of A and S laminin chains in SMCs of the intestine was developmentally regulated. Of the four beta 1-associated alpha integrin subunits that have been shown to recognize laminin (alpha 1, alpha 2, alpha 3, and alpha 6), only alpha 1 was revealed during the early fetal stage of development in smooth muscle of the arteries and digestive tract. alpha 3 appeared in aortic media only during the late fetal period. In adult arterial media and smooth muscle of the colon, alpha 1 and alpha 3 were the major potential laminin-binding integrins. The spatial-temporal distribution of laminin variants in developing and adult smooth muscle suggests that a variant laminin (possibly A-S-B2) interacting with its receptor (alpha 1 beta 1 or alpha 3 beta 1) may be important for maintenance of the differentiated SMC phenotype in vivo.
INSERM U127, Hopital Lariboisiere, Paris, France.
M
M
Glukhova
V
V
Koteliansky
C
C
Fondacci
F
F
Marotte
L
L
Rappaport
D000328:Adult; D002454:Cell Differentiation; D006801:Humans; D016023:Integrins / Q000032:analysis; D007797:Laminin / Q000032:analysis*; D046911:Macromolecular Substances; D009130:Muscle, Smooth / Q000737:chemistry* / Q000196:embryology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000196:embryology; D017474:Receptors, Laminin / Q000032:analysis*
D016023:Integrins; D007797:Laminin; D046911:Macromolecular Substances; D017474:Receptors, Laminin; C058783:laminin beta2