Related Experiment Video
Updated: Mar 6, 2026
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Blocking fibrotic signaling in fibroblasts from patients with carpal tunnel syndrome
Yoshiaki Yamanaka1, Anne Gingery1, Gosuke Oki1
1Biomechanics and Tendon & Soft Tissue Biology Laboratory, Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota.
Abstract:
Fibrosis of the subsynovial connective tissue (SSCT) in carpal tunnel syndrome (CTS) patients is increasingly recognized as an important aspect of CTS pathophysiology. 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 β1 (TGF-β1), and then treated either with a specific fibrosis pathway inhibitor targeting TGF-β receptor type 1 (TβRI), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), or vascular endothelial growth factor receptor (VEGFR). Fibrosis array and quantitative real-time polymerase chain reaction of fibrotic genes were evaluated. Array gene expression analysis revealed significant down-regulation of multiple fibrotic genes after treatment with TβRI, PDGFR, and VEGFR inhibitors. No array fibrotic genes were significantly down-regulated 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-regulation after TβRI inhibition. In contrast, VEGFR inhibition significantly down-regulated CTGF and SERPINE1, whereas, PDGFR and EGFR inhibition significantly down-regulated Col3. Taken together the inhibition of TβRI appears to be the primary mediator of fibrotic gene expression in fibroblasts from CTS patients. TGF-β/Smad activity was further evaluated, and as expected inhibition of Smad activity was significantly down-regulated after inhibition of TβRI, but not with PDGFR, VEGFR, or EGFR inhibition. These results indicate that local therapies specifically targeting TGF-β signaling alone or in combination offer the potential of a novel local antifibrosis therapy for patients with CTS.
Insights
Blocking transforming growth factor β1 (TGF-β1) receptor type 1 (TβRI) significantly reduced fibrotic gene expression in carpal tunnel syndrome (CTS) fibroblasts. This suggests TβRI inhibition is a promising local antifibrosis therapy for CTS.
Area of Science:
- Fibrosis research
- Carpal Tunnel Syndrome pathophysiology
- Cellular and molecular biology
Background:
- Fibrosis of the subsynovial connective tissue (SSCT) is a key factor in carpal tunnel syndrome (CTS).
- Understanding profibrotic pathways in SSCT fibroblasts is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the efficacy of inhibiting specific profibrotic pathways in SSCT fibroblasts from CTS patients.
- To identify the primary signaling pathway mediating fibrosis in CTS.
Main Methods:
- SSCT fibroblasts from CTS patients were stimulated with TGF-β1.
- Fibroblasts were treated with inhibitors targeting TβRI, PDGFR, EGFR, or VEGFR.
- Gene expression of fibrotic markers was analyzed using fibrosis arrays and quantitative real-time PCR.
Main Results:
- TβRI, PDGFR, and VEGFR inhibitors significantly down-regulated multiple fibrotic genes.
- TβRI inhibition primarily reduced fibrotic gene expression, including collagen type I A2 (Col1), collagen type III A1 (Col3), CTGF, and SERPINE1.
- EGFR inhibition did not significantly down-regulate any array fibrotic genes.
- TβRI inhibition also significantly reduced TGF-β/Smad activity.
Conclusions:
- Inhibition of TβRI is the primary mediator of fibrotic gene expression in SSCT fibroblasts from CTS patients.
- Targeting TGF-β signaling, particularly TβRI, offers potential as a novel local antifibrosis therapy for CTS.
