Upregulation of alpha(8)beta(1)-integrin in cardiac fibroblast by angiotensin II and transforming growth factor-beta1 |
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Authors: | Thibault G Lacombe M J Schnapp L M Lacasse A Bouzeghrane F Lapalme G |
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Institution: | 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 |
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Abstract: | Using a novel pharmacological tool with125I-echistatin to detect integrins on the cell, we haveobserved that cardiac fibroblasts harbor five different RGD-bindingintegrins: 8 1, 3 1, 5 1, v 1, and v 3.Stimulation of cardiac fibroblasts by angiotensin II (ANG II) ortransforming growth factor- 1 (TGF- 1) resulted in an increase ofprotein and heightening by 50% of the receptor density of 8 1-integrin. The effect of ANG II wasblocked by an AT1, but not an AT2, receptorantagonist, or by an anti-TGF- 1 antibody. ANG II and TGF- 1increased fibronectin secretion, smooth muscle -actin synthesis, andformation of actin stress fibers and enhanced attachment of fibroblaststo a fibronectin matrix. The 8- and 1-subunits were colocalized by immunocytochemistry with vinculin or 3-integrin at focal adhesion sites.These results indicate that 8 1-integrinis an abundant integrin on rat cardiac fibroblasts. Its positivemodulation by ANG II and TGF- 1 in a myofibroblast-likephenotype suggests the involvement of 8 1-integrin in extracellularmatrix protein deposition and cardiac fibroblast adhesion. |
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