AlphaV integrins play an important role in myofibroblast differentiation.
Transforming growth factor-beta1 is a potent mediator of the differentiation of fibroblasts into myofibroblasts, which is characterized by the appearance of the cytoskeletal protein alpha-smooth muscle actin. The aim of this study was to investigate the role of integrin extracellular matrix receptors in transforming growth factor-beta1-induced myofibroblast differentiation. We show that blockade of the alphav and/or beta1 integrins prevents the transforming growth factor-beta1-induced myofibroblast differentiation, seen by the increased expression of alpha-smooth muscle actin and enhanced collagen gel contraction in three human fibroblast cell lines (from the mouth, skin, and kidney). Further, blockade of alphav specific integrins alphavbeta5 and alphavbeta3 suppressed myofibroblast differentiation in fibroblasts from the mouth and skin; however, in the kidney cells, the prevention of differentiation was seen only with blockade of alphavbeta5 integrin but not alphavbeta3. A possible reason for this result may be different degrees of responsiveness to transforming growth factor-beta1 treatment seen from different anatomical origins of the cell lines. These data indicate a novel role for alphav integrins in the differentiation of human fibroblasts from the mouth, skin, and kidney into myofibroblasts and suggest that there is a common differentiation pathway.
Lygoe
Kate A
KA
Eastman Dental Institute, University College London, 256 Grays Inn Road, London WC1 X8LD, United Kingdom.
Norman
Jill T
JT
Marshall
John F
JF
Lewis
Mark P
MP
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D039564:Integrin alphaV / Q000502:physiology*; D039302:Integrin alphaVbeta3 / Q000502:physiology; D019012:Integrin beta1 / Q000502:physiology; D016023:Integrins / Q000502:physiology; D032446:Myoblasts / Q000166:cytology*; D051381:Rats; D019030:Receptors, Vitronectin / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D039564:Integrin alphaV; D039302:Integrin alphaVbeta3; D019012:Integrin beta1; D016023:Integrins; D019030:Receptors, Vitronectin; D016212:Transforming Growth Factor beta; C064660:integrin alphaVbeta5