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Dohi T, Miyake K, Aoki M, et al. Tissue Inhibitor of Metalloproteinase-2 Suppresses Collagen Synthesis in Cultured Keloid Fibroblasts. Plast Reconstr Surg Glob Open. 2015;3(9):e520doi: 10.1097/GOX.0000000000000503.
Dohi, T., Miyake, K., Aoki, M., Ogawa, R., Akaishi, S., Shimada, T., Okada, T., & Hyakusoku, H. (2015). Tissue Inhibitor of Metalloproteinase-2 Suppresses Collagen Synthesis in Cultured Keloid Fibroblasts. Plastic and reconstructive surgery. Global open, 3(9), e520. https://doi.org/10.1097/GOX.0000000000000503
Dohi, Teruyuki, et al. "Tissue Inhibitor of Metalloproteinase-2 Suppresses Collagen Synthesis in Cultured Keloid Fibroblasts." Plastic and reconstructive surgery. Global open vol. 3,9 (2015): e520. doi: https://doi.org/10.1097/GOX.0000000000000503
Dohi T, Miyake K, Aoki M, Ogawa R, Akaishi S, Shimada T, Okada T, Hyakusoku H. Tissue Inhibitor of Metalloproteinase-2 Suppresses Collagen Synthesis in Cultured Keloid Fibroblasts. Plast Reconstr Surg Glob Open. 2015 Sep 22;3(9):e520. doi: 10.1097/GOX.0000000000000503. eCollection 2015 Sep. PMID: 26495233; PMCID: PMC4596445.
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Plast Reconstr Surg Glob Open. 2015 Sep 22;3(9):e520. doi: 10.1097/GOX.0000000000000503. eCollection 2015 Sep.

Tissue Inhibitor of Metalloproteinase-2 Suppresses Collagen Synthesis in Cultured Keloid Fibroblasts.

Plastic and reconstructive surgery. Global open

Teruyuki Dohi, Koichi Miyake, Masayo Aoki, Rei Ogawa, Satoshi Akaishi, Takashi Shimada, Takashi Okada, Hiko Hyakusoku

Affiliations

  1. Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Tokyo, Japan; and Department of Biochemistry and Molecular Biology, Division of Gene Therapy, Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.

PMID: 26495233 PMCID: PMC4596445 DOI: 10.1097/GOX.0000000000000503

Abstract

BACKGROUND: Keloids are defined as a kind of dermal fibroproliferative disorder resulting from the accumulation of collagen. In the remodeling of extracellular matrix, the balance between matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) is as critical as the proper production of extracellular matrix. We investigate the role of TIMPs and MMPs in the pathogenesis of keloids and examine the therapeutic potential of TIMP-2.

METHODS: The expression of TIMPs and MMPs in most inflamed parts of cultured keloid fibroblasts (KFs) and peripheral normal skin fibroblasts (PNFs) in the same individuals and the reactivity of KFs to cyclic mechanical stretch were analyzed by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (n = 7). To evaluate the effect of treating KFs with TIMP-2, collagen synthesis was investigated by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, and microscopic analysis was used to examine the treatment effects of TIMP-2 on ex vivo cultures of keloid tissue (n = 6).

RESULTS: TIMP-2 was downregulated in cultured KFs compared with PNFs in the same individuals, and the reduction in TIMP-2 was exacerbated by cyclic mechanical stretch. Administration of TIMP-2 (200 or 300 ng/mL) significantly suppressed expression of Col1A2 and Col3A1 mRNA and collagen type I protein in KFs. TIMP-2 also significantly reduced the skin dermal and collagen bundle thickness in ex vivo cultures of keloid tissue.

CONCLUSION: These results indicated that downregulation of TIMP-2 in KFs is a crucial event in the pathogenesis of keloids, and the TIMP-2 would be a promising candidate for the treatment of keloids.

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