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In this study, we evaluated the effect of blocking profibrotic pathways in fibroblasts from the SSCT in CTS patients. Fibroblasts were stimulated with transforming growth factor \u03b21 (TGF\u2010\u03b21), and then treated either with a specific fibrosis pathway inhibitor targeting TGF\u2010\u03b2 receptor type 1 (T\u03b2RI), platelet\u2010derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), or vascular endothelial growth factor receptor (VEGFR). Fibrosis array and quantitative real\u2010time polymerase chain reaction of fibrotic genes were evaluated. Array gene expression analysis revealed significant down\u2010regulation of multiple fibrotic genes after treatment with T\u03b2RI, PDGFR, and VEGFR inhibitors. No array fibrotic genes were significantly down\u2010regulated with EGFR inhibition. Further gene expression analysis of known CTS fibrosis markers collagen type I A2 (Col1), collagen type III A1 (Col3), connective tissue growth factor (CTGF), and SERPINE1 showed significantly down\u2010regulation after T\u03b2RI inhibition. In contrast, VEGFR inhibition significantly down\u2010regulated CTGF and SERPINE1, whereas, PDGFR and EGFR inhibition significantly down\u2010regulated Col3. Taken together the inhibition of T\u03b2RI appears to be the primary mediator of fibrotic gene expression in fibroblasts from CTS patients. TGF\u2010\u03b2\/Smad activity was further evaluated, and as expected inhibition of Smad activity was significantly down\u2010regulated after inhibition of T\u03b2RI, but not with PDGFR, VEGFR, or EGFR inhibition. These results indicate that local therapies specifically targeting TGF\u2010\u03b2 signaling alone or in combination offer the potential of a novel local antifibrosis therapy for patients with CTS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25901","type":"journal-article","created":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T17:11:19Z","timestamp":1489165879000},"page":"2067-2074","source":"Crossref","is-referenced-by-count":21,"title":["Blocking fibrotic signaling in fibroblasts from patients with carpal tunnel syndrome"],"prefix":"10.1002","volume":"233","author":[{"given":"Yoshiaki","family":"Yamanaka","sequence":"first","affiliation":[{"name":"Biomechanics and Tendon &amp; Soft Tissue Biology Laboratory Department of Orthopedic Surgery Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Gingery","sequence":"additional","affiliation":[{"name":"Biomechanics and Tendon &amp; Soft Tissue Biology Laboratory Department of Orthopedic Surgery Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gosuke","family":"Oki","sequence":"additional","affiliation":[{"name":"Biomechanics and Tendon &amp; 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