title: TGF-β signaling regulates fibrotic expression and activity in carpal tunnel syndrome.
abstract: Fibrosis of the subsynovial connective tissue (SSCT) is a predominant feature of carpal tunnel syndrome (CTS). While the nature of CTS has been extensively studied, little is known about the etiology of this disease. We investigated SSCT tissue from patients with CTS and control subjects using fibrosis arrays and cell culture analysis. Twofold changes in fibrotic gene expression were found in multiple genes from patient SSCT using fibrosis arrays. This data was confirmed via qRT-PCR on a subset of genes; collagen I (Col1), collagen III (Col3), connective tissue growth factor (CTGF), transforming growth factor β (TGF-β), and SMAD3 (P < 0.05) which significantly corroborate the fold changes found in the fibrosis arrays. To further explore the nature of SSCT fibrosis, cells were isolated from patient and control tissue. Col1, Col3, TGF-β, and SMAD3 were highly expressed in patient SSCT fibroblasts as compared to control (P < 0.05). Further, fibrotic genes expression was decreased by inhibiting TGF-β receptor I (TβRI) activity (P < 0.05). TGF-β second messenger SMAD activity was significantly activated in SSCT fibroblasts from patients and this activation was abrogated by inhibiting TβRI signaling (P < 0.05). These findings suggest that blocking TGF-β signaling may be an important therapeutic approach to treating the underlying fibrosis of SSCT in CTS patients.
authors: Department of Biochemistry and Molecular Biology, Biomechanics and Tendon & Soft Tissue Biology Laboratory, Mayo Clinic, Rochester, Minnesota.
authors: Anne
authors: A
authors: Gingery
authors: Tai-Hua
authors: TH
authors: Yang
authors: Sandra M
authors: SM
authors: Passe
authors: Kai-Nan
authors: KN
authors: An
authors: Chunfeng
authors: C
authors: Zhao
authors: Peter C
authors: PC
authors: Amadio
mesh_terms: D000328:Adult; D001706:Biopsy; D002102:Cadaver; D002349:Carpal Tunnel Syndrome / Q000378:metabolism* / Q000503:physiopathology*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D005355:Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011621:Pteridines / Q000737:chemistry; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C526317:CCN2 protein, human; D024042:Collagen Type I; D024061:Collagen Type III; D011621:Pteridines; C511004:SD-208; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor
keywords: TGF-β; carpal tunnel syndrome; fibrosis; subsynovial connective tissue