The Role of Focal Adhesion Kinase in the TGF-β-Induced Myofibroblast Transdifferentiation of Human Tenon's Fibroblasts

Purpose To investigate the role of focal adhesion kinase (FAK) in transforming growth factor (TGF)-β-induced myofibroblast transdifferentiation of human Tenon's fibroblasts. Methods Primary cultured human Tenon's fibroblasts were exposed to TGF-β1 for up to 48 hours. The mRNA levels of FAK, α smooth muscle actin (αSMA), and β-actin were determined by quantitative real time reverse transcription polymerase chain reaction. The protein levels of collagen type I, FAK, phospho-FAK, αSMA, and β-actin were determined by Western immunoblots. After the small interfering RNA targeting FAK (siRNAFAK) molecules were delivered into the cells, the expressions of αSMA proteins were determined by Western immunoblots. Results In human Tenon's fibroblasts, TGF-β1 significantly increased the mRNA and protein expressions of αSMA. However, when the action of FAK was inhibited using siRNAFAK, the TGF-β1-induced expression of αSMA was attenuated. Conclusions Our data suggest that FAK may be associated with the TGF-β1-induced transdifferentiation of human Tenon's fibroblasts to myofibroblasts, which is the essential step of subconjunctival fibrosis.

[1]  G. Kouraklis,et al.  The role of focal adhesion kinase in early development. , 2010, Histology and histopathology.

[2]  D. Hedley,et al.  Targeting focal adhesion kinase signaling in tumor growth and metastasis , 2010, Expert opinion on therapeutic targets.

[3]  Samin Hong,et al.  TGF-β-induced interleukin-6 participates in transdifferentiation of human Tenon’s fibroblasts to myofibroblasts , 2009, Molecular vision.

[4]  S. Saika,et al.  TGF beta in fibroproliferative diseases in the eye. , 2009, Frontiers in bioscience.

[5]  C. Hofmann,et al.  Transforming growth factor-beta 1 induces intestinal myofibroblast differentiation and modulates their migration. , 2009, World journal of gastroenterology.

[6]  A. Rishi,et al.  TGF-beta1 modulates focal adhesion kinase expression in rat intestinal epithelial IEC-6 cells via stimulatory and inhibitory Smad binding elements. , 2009, Biochimica et biophysica acta.

[7]  G. Schlunck,et al.  Lovastatin inhibits TGF-beta-induced myofibroblast transdifferentiation in human tenon fibroblasts. , 2008, Investigative ophthalmology & visual science.

[8]  A. Rishi,et al.  Transforming growth factor-beta stimulates intestinal epithelial focal adhesion kinase synthesis via Smad- and p38-dependent mechanisms. , 2008, The American journal of pathology.

[9]  G. Schlunck,et al.  Localization of TGF-β type II receptor and ED-A fibronectin in normal conjunctiva and failed filtering blebs , 2008, Molecular vision.

[10]  P. Khaw,et al.  A phase III study of subconjunctival human anti-transforming growth factor beta(2) monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy. , 2007, Ophthalmology.

[11]  Christopher J. Parsons,et al.  Molecular mechanisms of hepatic fibrogenesis , 2007, Journal of gastroenterology and hepatology.

[12]  Yunliang Chen,et al.  FAK is required for TGFbeta-induced JNK phosphorylation in fibroblasts: implications for acquisition of a matrix-remodeling phenotype. , 2007, Molecular biology of the cell.

[13]  David S. Rogers,et al.  Combinatorial activation of FAK and AKT by transforming growth factor-beta1 confers an anoikis-resistant phenotype to myofibroblasts. , 2007, Cellular signalling.

[14]  C. Gladson,et al.  New concepts regarding focal adhesion kinase promotion of cell migration and proliferation , 2006, Journal of cellular biochemistry.

[15]  M. Buttmann,et al.  p38 inhibitors prevent TGF-beta-induced myofibroblast transdifferentiation in human tenon fibroblasts. , 2006, Investigative ophthalmology & visual science.

[16]  S. Saika,et al.  Interleukin-7 Modulates Extracellular Matrix Production and TGF-β Signaling in Cultured Human Subconjunctival Fibroblasts , 2006, Current eye research.

[17]  Neil O. Carragher,et al.  The role of focal-adhesion kinase in cancer — a new therapeutic opportunity , 2005, Nature Reviews Cancer.

[18]  M. Jinnin,et al.  Constitutive phosphorylation of focal adhesion kinase is involved in the myofibroblast differentiation of scleroderma fibroblasts. , 2005, The Journal of investigative dermatology.

[19]  J. Pulido,et al.  RNA interference targeting transforming growth factor-beta type II receptor suppresses ocular inflammation and fibrosis. , 2004, Molecular vision.

[20]  Giulio Gabbiani,et al.  The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. , 2004, The International journal of developmental biology.

[21]  P. Khaw,et al.  Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery. , 2003, Investigative ophthalmology & visual science.

[22]  R. Day,et al.  Myofibroblast Differentiation by Transforming Growth Factor-β1 Is Dependent on Cell Adhesion and Integrin Signaling via Focal Adhesion Kinase* , 2003, The Journal of Biological Chemistry.

[23]  Cordeiro Mf,et al.  Technology evaluation: lerdelimumab, Cambridge Antibody Technology. , 2003 .

[24]  B. Eyden Electron microscopy in the study of myofibroblastic lesions. , 2003, Seminars in diagnostic pathology.

[25]  B. Eyden The Myofibroblast: An Assessment of Controversial Issues and a Definition Useful in Diagnosis and Research , 2001, Ultrastructural pathology.

[26]  성공제,et al.  TGF-beta-induced interleukin-6 participates in transdifferentiation of human Tenon's fibroblasts to myofibroblasts , 2009 .

[27]  J. Pulido,et al.  RNA interference targeting transforming growth factor-β type II receptor suppresses ocular inflammation and fibrosis , 2004 .

[28]  M. Cordeiro Technology evaluation: lerdelimumab, Cambridge Antibody Technology. , 2003, Current opinion in molecular therapeutics (Print).