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Blocking fibrotic signaling in fibroblasts from patients with carpal tunnel syndrome.

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 ?1 (TGF-?1), and then treated either with a specific fibrosis pathway inhibitor targeting TGF-? receptor type 1 (T?RI), 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 T?RI, 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 T?RI 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 T?RI appears to be the primary mediator of fibrotic gene expression in fibroblasts from CTS patients. TGF-?/Smad activity was further evaluated, and as expected inhibition of Smad activity was significantly down-regulated after inhibition of T?RI, but not with PDGFR, VEGFR, or EGFR inhibition. These results indicate that local therapies specifically targeting TGF-? signaling alone or in combination offer the potential of a novel local antifibrosis therapy for patients with CTS.

SUBMITTER: Yamanaka Y

PROVIDER: S-EPMC5592125 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Blocking fibrotic signaling in fibroblasts from patients with carpal tunnel syndrome.

Yamanaka Yoshiaki Y Gingery Anne A Oki Gosuke G Yang Tai-Hua TH Zhao Chunfeng C Amadio Peter C PC

Journal of cellular physiology 20170503 3

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 rec ...[more]

PMID: 28294324

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Project description:Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper extremity. It is usually associated with the compression of the median nerve in the median groove. Because the main symptoms of CTS pain and numbness worsen at night, sleep disorders in CTS patients and the impact of preferred sleeping position on CTS development have been formerly studied. However, to the best of our knowledge, this is the first study assessing the frequency of CTS in obstructive sleep apnea (OSA) patients. This study aimed to determine the frequency of CTS in OSA patients and evaluate the causative relation between the two diseases.Records of individuals who were admitted to our sleep laboratory were retrospectively scanned. Eighty patients who were diagnosed with OSA and did not have comorbidities that might cause OSA (e.g., diabetes mellitus, hypothyroiditis, rheumatic diseases, and cervical radiculopathy) were included in the study along with 80 healthy controls who matched for age, sex, and BMI of OSA patients. To maintain observer blindness, patients were not questioned regarding their symptoms or the clinical data that would be used in the study. All participants underwent nerve conduction studies. Those who were diagnosed with CTS were questioned regarding CTS symptoms and the preferred sleeping position. Subsequently, patients were given the Boston CTS questionnaire.CTS frequency in OSA patients was found to be 27.5%. There was no significant relation between preferred sleeping position or being a manual worker and having CTS.CTS frequency in OSA patients is significantly higher than that in healthy individuals. In contrast to previous studies that have been performed in the absence of polysomnographic and electrophysiological data, in our study biomechanical factors were not associated with CTS presence. Therefore, we conclude that intermittent hypoxemia is the main etiological factor for CTS in OSA patients. Inflammation may be a common factor for etiopathogenesis for both diseases, but this hypothesis needs further investigation.

Dataset Information

Blocking fibrotic signaling in fibroblasts from patients with carpal tunnel syndrome.

Publications

Blocking fibrotic signaling in fibroblasts from patients with carpal tunnel syndrome.

Similar Datasets

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