av integrin is a Crucial Regulator in the Development of Dupuytren Contracture

  • Matsui Y
  • Kon S
  • Funakoshi T
  • et al.
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Abstract

Hypothesis: Although Dupuytren contracture is characterized by myofibroblast development and increased cytokines including transforming growth factor-ß1 (TGF-ß1) in the palmar fascia, the relationship between TGF-ß1 and av integrin, which is considered to be related to fibrosis, has not been clearly elucidated. We hypothesized that av integrin would play an important role in the development of Dupuytren contracture. Methods: Seven male patients whose mean age at the time of surgery was 70.7 years (range, 68 to 73) underwent partial fasciectomy as treatment for Dupuytren contracture. The nodule and cord were isolated from the palmar fascial tissues of the patients. Normal palmar fascia was obtained from seven control patients with carpal tunnel syndrome undergoing carpal tunnel release. These included two male and five female patients whose mean age at the time of surgery was 67.0 years (range, 36 to 88). Histologic and immunohistochemical analyses were performed to investigate the expression patterns of the myofibroblast and integrins. The expression of TGF-ß1 and av-, a4-, ß6-, ß8-integrins were assessed by real-time PCR reaction. Statistical comparisons were performed using paired t-tests (P < 0.05). Results: The spreading and proliferation of fibroblasts were found in nodules, while few fibroblasts were detected in cords and normal palmar fascia. In immunohistochemical analysis, alpha-smooth-muscle-actin (a-SMA)- positive cells were mainly observed in nodules, while few a-SMA-positive cells were found in normal palmar fascia. Among the a-SMA and integrins, a-SMA and av integrin were markedly induced and co-localized in nodules. Real-time PCR analysis confirmed that the expression of TGF-ß1 and av integrin genes were significantly increased in nodules, as compared to those in normal palmar fascia (P = 0.004 and P = 0.006, respectively) (Figure 1A and 1B). Summary: Henderson et al. showed that av integrin controls a core molecular pathway that regulates fibrosis in several organs. In fact, we found the expression of TGF-ß1 and av integrin were significantly increased in nodules, as compared to those in normal fascia. The obtained results indicate that av integrin is a critical intrinsic regulator of the growth of fibrous tissue in Dupuytren contracture via regulating TGF-ß1 expression. av integrin will become a target molecule for the injection treatment of Dupuytren contracture.

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Matsui, Y., Kon, S., Funakoshi, T., Miyashita, T., Matsuda, T., & Iwasaki, N. (2015). av integrin is a Crucial Regulator in the Development of Dupuytren Contracture. The Journal of Hand Surgery, 40(9), e46–e47. https://doi.org/10.1016/j.jhsa.2015.06.079

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