Transforming growth factor-β (TGF-β) expression is increased in the subsynovial connective tissues of patients with idiopathic carpal tunnel syndrome

Abstract

Non-inflammatory fibrosis of the subsynovial connective tissue (SSCT) is a hallmark of carpal tunnel syndrome (CTS). The etiology of this finding and its relationship to the development of CTS remain poorly understood. Recent studies have found that transforming growth factor-β (TGF-β) plays a central role in fibrosis. The purpose of this study was to investigate the expression of TGF-β and connective tissue growth factor (CTGF), a downstream mediator of TGF-β, in the pathogenesis of CTS. We compared SSCT specimens from 26 idiopathic CTS patients with specimens from 10 human cadaver controls with no previous diagnosis of CTS. Immunohistochemistry was performed to determine levels TGF-β1, CTGF, collagen 1(Col1) and collagen 3 (Col3) expression. TGF-β1 (p < 0.01), CTGF (p < 0.01), and Col3 (p < 0.01) were increased in SSCT of CTS patients compared with control tissue. In addition, a strong positive correlation was found between TGF-β1 and CTGF, (R(2) = 0.80, p < 0.01) and a moderate positive correlation between Col3 and TGF-β1 (R(2) = 0.49, p < 0.01). These finding suggest that there is an increased expression of TGF-β and CTGF, a TGF-β regulated protein, and that this TGF-β activation may be responsible for SSCT fibrosis in CTS patients.

Keywords: CTGF; TGF-β; carpal tunnel syndrome; subsynovial connective tissue.

Figure 1

TGF-β1 positive cells were identified in SSCT (A and B) in the CTS patients. In the controls, there were few TGF-β1 positive cells in SSCT(C and D). There were significantly more TGF-β1 positive cells in the CTS patients than in the controls (E).

Figure 2

CTGF positive cells were identified in SSCT (A and B). There were few CTGF positive cells in the SSCT (C and D) in the control group. There were significantly more CTGF positive cells in the CTS patient than in the controls (E).

Figure 3

Comparison of the Col1 (A) and Col3 (B) positive area between CTS patients and controls. There was no difference in Col1 positive area comparing CTS patient and controls (A), but the Col3 positive area in the CTS patients was significantly larger than that in the controls (B).

Figure 4

Spearman rank order correlation coefficient between TGF-β1, CTGF, Col1 and Col3. A strong positive correlation were found between TGF-β1 and CTGF(A), moderate positive correlation between Col3 and TGF-β1 (B), Col3 and CTGF (C), low positive correlation between Col1 and TGF-β (D) and Col1, and CTGF (E).