Upregulation of alpha(8)beta(1)-integrin in cardiac fibroblast by angiotensin II and transforming growth factor-beta1.
Using a novel pharmacological tool with (125)I-echistatin to detect integrins on the cell, we have observed that cardiac fibroblasts harbor five different RGD-binding integrins: alpha(8)beta(1), alpha(3)beta(1), alpha(5)beta(1), alpha(v)beta(1), and alpha(v)beta(3). Stimulation of cardiac fibroblasts by angiotensin II (ANG II) or transforming growth factor-beta1 (TGF-beta1) resulted in an increase of protein and heightening by 50% of the receptor density of alpha(8)beta(1)-integrin. The effect of ANG II was blocked by an AT(1), but not an AT(2), receptor antagonist, or by an anti-TGF-beta1 antibody. ANG II and TGF-beta1 increased fibronectin secretion, smooth muscle alpha-actin synthesis, and formation of actin stress fibers and enhanced attachment of fibroblasts to a fibronectin matrix. The alpha(8)- and beta(1)-subunits were colocalized by immunocytochemistry with vinculin or beta(3)-integrin at focal adhesion sites. These results indicate that alpha(8)beta(1)-integrin is an abundant integrin on rat cardiac fibroblasts. Its positive modulation by ANG II and TGF-beta1 in a myofibroblast-like phenotype suggests the involvement of alpha(8)beta(1)-integrin in extracellular matrix protein deposition and cardiac fibroblast adhesion.
Thibault
G
G
Multidisciplinary Research Group in Hypertension of the Canadian Institutes of Health Research, Institut de Recherches Cliniques de Montréal, Montreal, Quebec, Canada H2W 1R7. thibaug@ircm.qc.ca
Lacombe
M J
MJ
Schnapp
L M
LM
Lacasse
A
A
Bouzeghrane
F
F
Lapalme
G
G
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D016023:Integrins / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019138:Antibodies, Blocking; D005353:Fibronectins; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014662:Vasoconstrictor Agents; C094866:integrin alpha8beta1; D000804:Angiotensin II; C057986:echistatin