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Depletion of polyamines and increase of transforming growth factor-beta1, c-myc, collagen-type I, matrix metalloproteinase-1, and metalloproteinase-2 mRNA in primary human gingival fibroblasts.
J Periodontol. 2005 Mar; 76(3):443-9.JP

Abstract

BACKGROUND

The polyamines spermidine, spermine, and putrescine are known to be deeply linked with growth processes, gene expression, and extracellular matrix synthesis. Their cellular content depends primarily on the activity of the enzyme ornithine decarboxylase. High levels of ornithine decarboxylase and polyamines have been found in proliferative, inflammatory, and neoplastic pathologies of the oral cavity and in gingival fluid. Difluoromethylornithine (DFMO) selectively inhibits ornithine decarboxylase, thus depleting polyamine content and preventing cell proliferation and synthesis activity. The aim of this study was to investigate whether DFMO treatment could modify the genes involved in cell proliferation and extracellular matrix turnover.

METHODS

Fibroblasts derived from non-inflamed gingiva were maintained in Dulbecco's modified Eagle's medium (DMEM) plus alpha-difluoromethylornithine for 4 days. At 0, 24, 48, 72, and 96 hours cell number was assessed, polyamine levels were quantified with high performance liquid chromatography (HPLC) method, and transforming growth factor-beta1 (TGF-beta1), c-myc, matrix metalloproteinases (MMP)-1 and 2, collagen type I (COL-I) and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were evaluated by reverse transcription polymerase chain reaction (RT-PCR).

RESULTS

Fibroblasts treated with DFMO significantly decreased cell proliferation, ornithine decarboxylase activity, and putrescine levels at all treatment times, spermidine after 72 and 96 hours, and spermine after 96 hours of culture. Total polyamines decreased (P < or =0.01) at 96 hours after DFMO treatment, while c-myc, TGF-beta1, MMP-1 and 2, COL-I mRNA significantly increased. Conversely, TIMP-1 did not show any significant change. The polyamines trend was not correlated to c-myc, TGF-beta1, MMP-1 and -2, and TIMP-1 mRNA levels. Transforming growth factor-beta1 and c-myc mRNA expression were related and correlated to MMP-1 and 2, COL-I and TIMP-1 mRNA trend after DFMO treatment.

CONCLUSIONS

Our data show that as the polyamine content decreases, TGF-beta1, c-myc, MMP-1 and -2, and COL-I mRNA levels increase, therefore a negative regulatory role of the polyamines on the mRNA expression could be suggested.

Authors+Show Affiliations

Department of Human Morphology-Interdisciplinary Laboratories of Advanced Technologies, Segrate, University of Milan, Milan, Italy. giordano.stabellini@unimi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15857080

Citation

Stabellini, Giordano, et al. "Depletion of Polyamines and Increase of Transforming Growth Factor-beta1, C-myc, Collagen-type I, Matrix Metalloproteinase-1, and Metalloproteinase-2 mRNA in Primary Human Gingival Fibroblasts." Journal of Periodontology, vol. 76, no. 3, 2005, pp. 443-9.
Stabellini G, Moscheni C, Gagliano N, et al. Depletion of polyamines and increase of transforming growth factor-beta1, c-myc, collagen-type I, matrix metalloproteinase-1, and metalloproteinase-2 mRNA in primary human gingival fibroblasts. J Periodontol. 2005;76(3):443-9.
Stabellini, G., Moscheni, C., Gagliano, N., Dellavia, C., Calastrini, C., Ferioli, M. E., & Gioia, M. (2005). Depletion of polyamines and increase of transforming growth factor-beta1, c-myc, collagen-type I, matrix metalloproteinase-1, and metalloproteinase-2 mRNA in primary human gingival fibroblasts. Journal of Periodontology, 76(3), 443-9.
Stabellini G, et al. Depletion of Polyamines and Increase of Transforming Growth Factor-beta1, C-myc, Collagen-type I, Matrix Metalloproteinase-1, and Metalloproteinase-2 mRNA in Primary Human Gingival Fibroblasts. J Periodontol. 2005;76(3):443-9. PubMed PMID: 15857080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Depletion of polyamines and increase of transforming growth factor-beta1, c-myc, collagen-type I, matrix metalloproteinase-1, and metalloproteinase-2 mRNA in primary human gingival fibroblasts. AU - Stabellini,Giordano, AU - Moscheni,Claudia, AU - Gagliano,Nicoletta, AU - Dellavia,Claudia, AU - Calastrini,Carla, AU - Ferioli,Maria Elena, AU - Gioia,Magda, PY - 2005/4/29/pubmed PY - 2005/6/23/medline PY - 2005/4/29/entrez SP - 443 EP - 9 JF - Journal of periodontology JO - J Periodontol VL - 76 IS - 3 N2 - BACKGROUND: The polyamines spermidine, spermine, and putrescine are known to be deeply linked with growth processes, gene expression, and extracellular matrix synthesis. Their cellular content depends primarily on the activity of the enzyme ornithine decarboxylase. High levels of ornithine decarboxylase and polyamines have been found in proliferative, inflammatory, and neoplastic pathologies of the oral cavity and in gingival fluid. Difluoromethylornithine (DFMO) selectively inhibits ornithine decarboxylase, thus depleting polyamine content and preventing cell proliferation and synthesis activity. The aim of this study was to investigate whether DFMO treatment could modify the genes involved in cell proliferation and extracellular matrix turnover. METHODS: Fibroblasts derived from non-inflamed gingiva were maintained in Dulbecco's modified Eagle's medium (DMEM) plus alpha-difluoromethylornithine for 4 days. At 0, 24, 48, 72, and 96 hours cell number was assessed, polyamine levels were quantified with high performance liquid chromatography (HPLC) method, and transforming growth factor-beta1 (TGF-beta1), c-myc, matrix metalloproteinases (MMP)-1 and 2, collagen type I (COL-I) and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were evaluated by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Fibroblasts treated with DFMO significantly decreased cell proliferation, ornithine decarboxylase activity, and putrescine levels at all treatment times, spermidine after 72 and 96 hours, and spermine after 96 hours of culture. Total polyamines decreased (P < or =0.01) at 96 hours after DFMO treatment, while c-myc, TGF-beta1, MMP-1 and 2, COL-I mRNA significantly increased. Conversely, TIMP-1 did not show any significant change. The polyamines trend was not correlated to c-myc, TGF-beta1, MMP-1 and -2, and TIMP-1 mRNA levels. Transforming growth factor-beta1 and c-myc mRNA expression were related and correlated to MMP-1 and 2, COL-I and TIMP-1 mRNA trend after DFMO treatment. CONCLUSIONS: Our data show that as the polyamine content decreases, TGF-beta1, c-myc, MMP-1 and -2, and COL-I mRNA levels increase, therefore a negative regulatory role of the polyamines on the mRNA expression could be suggested. SN - 0022-3492 UR - https://www.unboundmedicine.com/medline/citation/15857080/Depletion_of_polyamines_and_increase_of_transforming_growth_factor_beta1_c_myc_collagen_type_I_matrix_metalloproteinase_1_and_metalloproteinase_2_mRNA_in_primary_human_gingival_fibroblasts_ L2 - https://doi.org/10.1902/jop.2005.76.3.443 DB - PRIME DP - Unbound Medicine ER -