title: FAK activity is required for HGF to suppress TGF-β1-induced cellular proliferation.
abstract: Due to the complex nature of the tendon architecture, the regeneration of these tissues results in the formation of scars. As a direct result of scar formation, the ability of the tendon tissues to function is impaired and often results in further damage that has been afflicted to the tendon architecture. The growth and proliferation of tendon fibroblasts involve a complex network of signalling molecules. To understand and aid in the proper repair of this complex tissue network, a more in-depth understanding is required in the events that induce the growth of tendon cells. Several studies have shown the apoptotic mechanisms induced by the mitogen, hepatocyte growth factor, in multiple biological and pathological systems. In our recent research, we have described a mechanism where hepatocyte growth factor (HGF) is able to inhibit the proliferative effects of transforming growth factor-β1 (TGF-β1) and induce apoptosis in rat tendon fibroblasts. Transforming growth factor-β1 is able to induce the proliferation of fibroblast cells by increasing both the gene expression and protein levels of α-smooth muscle actin (α-SMA) and c-MET. We have also shown that inhibition of extracellular signal-regulated kinase 1/2 does not block hepatocyte growth factor-induced growth arrest. However, we have shown that blocking the activity of focal adhesion kinase can prevent the growth inhibition ability of hepatocyte growth factor in tendon fibroblasts. Collectively, our studies show growth inhibitory pathway in tendon fibroblasts induced by hepatocyte growth factor and mediated focal adhesion kinase.
authors.affiliation: Pediatric Orthopedics Unit, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150001, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150086, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150086, China.
authors.forename: Sulong
authors.initials: S
authors.lastname: Yang
authors.affiliation: Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150086, China.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150086, China. zhaozhu247@163.com.
authors.forename: Zhaozhu
authors.initials: Z
authors.lastname: Li
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D015363:Quinolones / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology; D013710:Tendons / Q000166:cytology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000199:Actins; D051417:Focal Adhesion Kinase 1; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D015363:Quinolones; D013450:Sulfones; D053773:Transforming Growth Factor beta1; C521108:6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; C498862:Acta2 protein, rat; C496052:Ptk2 protein, rat
keywords: FAK; Hepatocyte growth factor; Tendon fibroblast; Transforming growth factor-β1