헤파린이 수근관 증후 군 환자의 횡수근 인대에서 추출한 섬유아세포의 콜라겐, MMP 및 TGF-β 동위형 발현에 미치는 영향

The Effect of Heparin on Gene Expression of Collagen, MMP, TGF-β Isoforms Using Cultured Fibroblast from Transverse Carpal Ligament of Carpal Tunnel Syndrome

  • 정성호 (고려대학교 의과대학 성형외과학교실) ;
  • 나민화 (이화여자대학교 의과대학 성형외과학교실) ;
  • 이재선 (고려대학교 의과대학 성형외과학교실) ;
  • 송상훈 (고려대학교 의과대학 성형외과학교실) ;
  • 윤을식 (고려대학교 의과대학 성형외과학교실) ;
  • 동은상 (고려대학교 의과대학 성형외과학교실) ;
  • 김한중 (이화여자대학교 의과대학 성형외과학교실)
  • Jeong, Seong Ho (Department of Plastic and Renconstructive Surgery, Korea University College of Medicine) ;
  • Na, Min Hwa (Department of Plastic and Reconstructive Surgery, Ehwa Wemen's University College of Medicine) ;
  • Lee, Jae Sun (Department of Plastic and Renconstructive Surgery, Korea University College of Medicine) ;
  • Song, Sang Hun (Department of Plastic and Renconstructive Surgery, Korea University College of Medicine) ;
  • Yoon, Eul Sik (Department of Plastic and Renconstructive Surgery, Korea University College of Medicine) ;
  • Dhong, Eun Sang (Department of Plastic and Renconstructive Surgery, Korea University College of Medicine) ;
  • Kim, Han Joong (Department of Plastic and Reconstructive Surgery, Ehwa Wemen's University College of Medicine)
  • 투고 : 2006.03.08
  • 발행 : 2006.07.10

초록

Purpose: Noninflammatory synovial fibrosis has been noted for main causal factor of carpal tunnel syndrome (CTS). Recently, there are some reports that heparin have not only anti-coagulative effect but also anti-inflammatory and anti-fibrotic potential and have an effect on interstitial pulmonary fiborosis. Authors examined whether heparin affects pathogenesis of CTS. Methods: First, heparin was administered to fibroblast that was cultured from patient's transverse carpal ligament. Secondly, we evaluated the expression from genes of type I, III collagen, TGF ${\beta}$ isoforms and MMP. Fibroblasts were isolated and cultured from transverse carpal ligaments of 5 patients with CTS. Heparin (0, 1, 10,$100{\mu}g/ml$) was administered to cultured fibroblast and reverse transcription PCR for mRNA expression of type I, III collagen, TGF-${\beta}$ isoforms and MMP was done. Results: Heparin suppressed gene expression of type I, III collagen and TGF-${\beta}1$, ${\beta}3$ but promoted gene expression of TGF-${\beta}2$ and MMP-2. Conclusion: Heparin directly suppress gene expression of type I, III collagen. But, It is undetermined that heparin can present it's effect mediated by TGF ${\beta}$ isoforms or MMP.

키워드

참고문헌

  1. Stransky G, Weis S, Neumuller J, Hakimzadeh A, Fimeis F, Arruner K, Partsch G, Eberl R: Morphometric analysis of collagen fibrils in idiopathic carpal tunnel syndrome. Exp Cell Biol 55: 57, 1987
  2. Weis S, Stransky G, Dimitrov L, Wenger E, Neumuller J, Hakimzadeh A, Fimeis F, Partsch G, Eberl R: Morphometric analysis of collagen fibrils in idiopathic carpal tunnel syndrome: Part2. Exp Cell Biol 55: 179, 1987
  3. Scelsi R, Zanlungo M, Tenti P: Carpal tunnel syndrome. Anatomical and clinical correlations and morphological and ultrastructural aspects of the tenosynovial sheath. Ital J Orihop Traumatol 15: 75, 1989
  4. Freeland AE, Tucci MA, Barbieri RA, Angel MF, Nick TG: Biochemical evaluation of serum and flexor tenosynovium in carpal tunnel syndrome. Microsurgery 22: 378, 2002 https://doi.org/10.1002/micr.10065
  5. Miyasaka N, Sato K, Kitano Y, Higaki M, Nishioka K, Ohta K: Aberrant cytokine production from tenosynovium in dialysis associated amyloidosis. Ann Rheum Dis 51: 797, 1992 https://doi.org/10.1136/ard.51.6.797
  6. Takasu S, Takatsu S, Kunitomo K, Kokumai Y: Serum hyaluronic acid and interleukin-6 as possible markers of carpal tunnel syndrome in chronic hemodialysis patients. Artif Organs 18: 420, 1992
  7. Frizelle S, Schwarz J, Huber SA, Leslie K: Evaluation of the effects of low molecular weight heparin on inflammation and collagen deposition in chronic coxsackievirus B3-induced myocarditis in A/J mice. Am J Pathol 141: 203, 1992
  8. Mousa SA, Mohamed S: Anti-angiogenic mechanisms and efficacy of the low molecular weight heparin, tinzaparin: anti-cancer efficacy. Oncol Rep 12: 683, 2004
  9. Yard BA, Chorianopoulos E, Herr D, van der Woude FJ: Regulation of endothelin-1 and transforming growth factor-$\beta_1$ production in cultured proximal tubular cells by albumin and heparan sulphate glycosaminoglycans. Nephrol Dial Transplant 16: 1769, 2001 https://doi.org/10.1093/ndt/16.9.1769
  10. Okona-Mensah KB, Shittu E, Page C, Costello J, Kilfeather SA: Inhibition of serum and transforming growth factor$\beta$ (TGF-$\beta_1$)-induced DNA synthesis in confluent airway smooth muscle by heparin. Br J Pharmacol 125: 599, 1998 https://doi.org/10.1038/sj.bjp.0702046
  11. Shi J, Hao JH, Ren WH, Zhu JR: Effects of heparin on liver fibrosis in patients with chronic hepatitis B. World J Gastroenterol 9: 1611, 2003 https://doi.org/10.3748/wjg.v9.i7.1611
  12. Mogford JE, Tawil N, Olen A, Gies D, Xia Y, Mustoe TA: Effect of age and hypoxia on TGF $\beta_1$ receptor expression and signal transduction in human dermal fibroblasts: impact on cell migration. J Cell Physiol 190: 259, 2002 https://doi.org/10.1002/jcp.10060
  13. Hosokawa R, Nonaka K, Morifuji M, Shum L, Ohishi M: TGF-$\beta_3$ decreases type I collagen and scarring after labioplasty. J Dent Res 82: 558, 2003 https://doi.org/10.1177/154405910308200714
  14. Parks We: Matrix metalloproteinases in lung repair. Eur Respir J Suppl 44: 36s, 2003
  15. Agren MS: Gelatinase activity during wound healing. Br J Dermatol 131: 634, 1994 https://doi.org/10.1111/j.1365-2133.1994.tb04974.x