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Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration.
Br J Dermatol. 2005 Aug; 153(2):295-300.BJ

Abstract

BACKGROUND

A keloid is a specific skin lesion that expands beyond the boundaries of the original injury as it heals. Histologically, it is characterized by the excessive accumulation of collagen. However, the reasons for the expansion and the invasive nature of keloids remain unknown.

OBJECTIVES

We evaluated collagen degradation and migration by cultured keloid fibroblasts based on the assumption that these variables were of functional relevance to the expanding and invasive nature of keloid lesions.

METHODS

Collagen production was investigated by the detection of type 1 collagen (procollagen type 1C peptide: P1P). Matrix metalloproteinase (MMP)-1 (interstitial collagenase) and MMP-2 (gelatinase-A), were investigated as elements of the collagen degradation system. Enzyme immunoassays were performed to measure the production of P1P, MMP-1, MMP-2, and tissue inhibitor of metalloproteinase (TIMP)-1. To assess the production of MMP-2 its gelatinolytic activity was measured by zymography using gelatin-containing gels. The participation of transforming growth factor-beta1 (TGF-beta1) in the production and degradation of collagen was also investigated. Finally, the migratory activity of keloid fibroblasts was evaluated using a colony dispersion assay.

RESULTS

The production of type 1 collagen, MMP-1, MMP-2, and TIMP-1 by keloid fibroblasts was 3-fold, 6-fold, 2.4-fold, and 2-fold greater than that of normal dermal fibroblasts, respectively. Production of P1P was increased when TGF-beta1 was added to cultures of keloid fibroblasts, while it was decreased when anti-TGF-beta1 antibody was added to the cultures. In contrast, the production of MMP-1 was decreased by the addition of TGF-beta1 to cultured keloid fibroblasts, while it was increased when anti-TGF-beta1 antibody was added to the cultures. The production of MMP-2 increased after treatment with TGF-beta1, but did not change significantly when anti-TGF-beta1 antibody was added to the cultures. Production of TIMP-1 did not change significantly when either TGF-beta1 or anti-TGF-beta1 antibody was added to the cultures. Keloid fibroblasts showed a 2.5-fold increase of migratory activity compared with normal dermal fibroblasts, while the migratory activity of these fibroblasts was reduced to the control level by treatment with a broad-spectrum MMP inhibitor (GM 6001).

CONCLUSIONS

Cultured keloid fibroblasts showed increased production of collagen and MMPs, and TGF-beta1 played a role in this regulation of production. In addition, increased production of MMPs had a role in the high migratory activity of cultured keloid fibroblasts.

Authors+Show Affiliations

Department of Plastic and Reconstructive Surgery, Tenri Hospital, 200 Mishima, Tenri, Nara, 632-8552, Japan. masofuj@mth.biglobe.ne.jpNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16086739

Citation

Fujiwara, M, et al. "Keloid-derived Fibroblasts Show Increased Secretion of Factors Involved in Collagen Turnover and Depend On Matrix Metalloproteinase for Migration." The British Journal of Dermatology, vol. 153, no. 2, 2005, pp. 295-300.
Fujiwara M, Muragaki Y, Ooshima A. Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. Br J Dermatol. 2005;153(2):295-300.
Fujiwara, M., Muragaki, Y., & Ooshima, A. (2005). Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. The British Journal of Dermatology, 153(2), 295-300.
Fujiwara M, Muragaki Y, Ooshima A. Keloid-derived Fibroblasts Show Increased Secretion of Factors Involved in Collagen Turnover and Depend On Matrix Metalloproteinase for Migration. Br J Dermatol. 2005;153(2):295-300. PubMed PMID: 16086739.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. AU - Fujiwara,M, AU - Muragaki,Y, AU - Ooshima,A, PY - 2005/8/10/pubmed PY - 2005/10/27/medline PY - 2005/8/10/entrez SP - 295 EP - 300 JF - The British journal of dermatology JO - Br J Dermatol VL - 153 IS - 2 N2 - BACKGROUND: A keloid is a specific skin lesion that expands beyond the boundaries of the original injury as it heals. Histologically, it is characterized by the excessive accumulation of collagen. However, the reasons for the expansion and the invasive nature of keloids remain unknown. OBJECTIVES: We evaluated collagen degradation and migration by cultured keloid fibroblasts based on the assumption that these variables were of functional relevance to the expanding and invasive nature of keloid lesions. METHODS: Collagen production was investigated by the detection of type 1 collagen (procollagen type 1C peptide: P1P). Matrix metalloproteinase (MMP)-1 (interstitial collagenase) and MMP-2 (gelatinase-A), were investigated as elements of the collagen degradation system. Enzyme immunoassays were performed to measure the production of P1P, MMP-1, MMP-2, and tissue inhibitor of metalloproteinase (TIMP)-1. To assess the production of MMP-2 its gelatinolytic activity was measured by zymography using gelatin-containing gels. The participation of transforming growth factor-beta1 (TGF-beta1) in the production and degradation of collagen was also investigated. Finally, the migratory activity of keloid fibroblasts was evaluated using a colony dispersion assay. RESULTS: The production of type 1 collagen, MMP-1, MMP-2, and TIMP-1 by keloid fibroblasts was 3-fold, 6-fold, 2.4-fold, and 2-fold greater than that of normal dermal fibroblasts, respectively. Production of P1P was increased when TGF-beta1 was added to cultures of keloid fibroblasts, while it was decreased when anti-TGF-beta1 antibody was added to the cultures. In contrast, the production of MMP-1 was decreased by the addition of TGF-beta1 to cultured keloid fibroblasts, while it was increased when anti-TGF-beta1 antibody was added to the cultures. The production of MMP-2 increased after treatment with TGF-beta1, but did not change significantly when anti-TGF-beta1 antibody was added to the cultures. Production of TIMP-1 did not change significantly when either TGF-beta1 or anti-TGF-beta1 antibody was added to the cultures. Keloid fibroblasts showed a 2.5-fold increase of migratory activity compared with normal dermal fibroblasts, while the migratory activity of these fibroblasts was reduced to the control level by treatment with a broad-spectrum MMP inhibitor (GM 6001). CONCLUSIONS: Cultured keloid fibroblasts showed increased production of collagen and MMPs, and TGF-beta1 played a role in this regulation of production. In addition, increased production of MMPs had a role in the high migratory activity of cultured keloid fibroblasts. SN - 0007-0963 UR - https://www.unboundmedicine.com/medline/citation/16086739/Keloid_derived_fibroblasts_show_increased_secretion_of_factors_involved_in_collagen_turnover_and_depend_on_matrix_metalloproteinase_for_migration_ L2 - https://doi.org/10.1111/j.1365-2133.2005.06698.x DB - PRIME DP - Unbound Medicine ER -