Tags

Type your tag names separated by a space and hit enter

Transcription factor early growth response 1 activity up-regulates expression of tissue inhibitor of metalloproteinases 1 in human synovial fibroblasts.
Arthritis Rheum. 2003 Feb; 48(2):348-59.AR

Abstract

OBJECTIVE

To investigate the regulatory potential of early growth response 1 (Egr-1) on tissue inhibitor of metalloproteinases 1 (TIMP-1) expression in synovial fibroblasts.

METHODS

Egr-1 and TIMP-1 transcripts were detected by in situ hybridization in synovial tissue. Egr-1-regulated TIMP expression was studied in immortalized fibroblast lines using gel retardation assays, RNase protection analysis, reporter gene studies using the human TIMP-1 promoter, and by enzyme-linked immunosorbent assay.

RESULTS

TIMP-1 and Egr-1 were coexpressed in synovial fibroblasts of inflamed joints, and Egr-1 activated the expression of TIMP-1. Egr-1 binding to a recognition sequence in the TIMP-1 promoter was demonstrated in gel retardation and reporter gene assays. Since the same DNA sequence was also recognized by the transcription factor Sp-1, our results suggest that the expression of TIMP-1 in synovial fibroblasts may be differentially regulated by Egr-1 and Sp-1. In addition, fibroblasts expressing Egr-1 at high levels were found to express increased levels of TIMP-2 and TIMP-3 messenger RNA.

CONCLUSION

The enhanced expression of Egr-1 may regulate the activity of matrix metalloproteinases in synovial fibroblasts by enhancing the expression of the TIMP-1, -2, and -3 genes.

Authors+Show Affiliations

University Hospital Tubingen, Tubingen, Germany.No affiliation info availableNo 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

12571843

Citation

Aicher, Wilhelm K., et al. "Transcription Factor Early Growth Response 1 Activity Up-regulates Expression of Tissue Inhibitor of Metalloproteinases 1 in Human Synovial Fibroblasts." Arthritis and Rheumatism, vol. 48, no. 2, 2003, pp. 348-59.
Aicher WK, Alexander D, Haas C, et al. Transcription factor early growth response 1 activity up-regulates expression of tissue inhibitor of metalloproteinases 1 in human synovial fibroblasts. Arthritis Rheum. 2003;48(2):348-59.
Aicher, W. K., Alexander, D., Haas, C., Kuchen, S., Pagenstecher, A., Gay, S., Peter, H. H., & Eibel, H. (2003). Transcription factor early growth response 1 activity up-regulates expression of tissue inhibitor of metalloproteinases 1 in human synovial fibroblasts. Arthritis and Rheumatism, 48(2), 348-59.
Aicher WK, et al. Transcription Factor Early Growth Response 1 Activity Up-regulates Expression of Tissue Inhibitor of Metalloproteinases 1 in Human Synovial Fibroblasts. Arthritis Rheum. 2003;48(2):348-59. PubMed PMID: 12571843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcription factor early growth response 1 activity up-regulates expression of tissue inhibitor of metalloproteinases 1 in human synovial fibroblasts. AU - Aicher,Wilhelm K, AU - Alexander,Dorothea, AU - Haas,Christian, AU - Kuchen,Stefan, AU - Pagenstecher,Axel, AU - Gay,Steffen, AU - Peter,Hans-Hartmut, AU - Eibel,Hermann, PY - 2003/2/7/pubmed PY - 2003/3/14/medline PY - 2003/2/7/entrez SP - 348 EP - 59 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 48 IS - 2 N2 - OBJECTIVE: To investigate the regulatory potential of early growth response 1 (Egr-1) on tissue inhibitor of metalloproteinases 1 (TIMP-1) expression in synovial fibroblasts. METHODS: Egr-1 and TIMP-1 transcripts were detected by in situ hybridization in synovial tissue. Egr-1-regulated TIMP expression was studied in immortalized fibroblast lines using gel retardation assays, RNase protection analysis, reporter gene studies using the human TIMP-1 promoter, and by enzyme-linked immunosorbent assay. RESULTS: TIMP-1 and Egr-1 were coexpressed in synovial fibroblasts of inflamed joints, and Egr-1 activated the expression of TIMP-1. Egr-1 binding to a recognition sequence in the TIMP-1 promoter was demonstrated in gel retardation and reporter gene assays. Since the same DNA sequence was also recognized by the transcription factor Sp-1, our results suggest that the expression of TIMP-1 in synovial fibroblasts may be differentially regulated by Egr-1 and Sp-1. In addition, fibroblasts expressing Egr-1 at high levels were found to express increased levels of TIMP-2 and TIMP-3 messenger RNA. CONCLUSION: The enhanced expression of Egr-1 may regulate the activity of matrix metalloproteinases in synovial fibroblasts by enhancing the expression of the TIMP-1, -2, and -3 genes. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/12571843/Transcription_factor_early_growth_response_1_activity_up_regulates_expression_of_tissue_inhibitor_of_metalloproteinases_1_in_human_synovial_fibroblasts_ L2 - https://doi.org/10.1002/art.10774 DB - PRIME DP - Unbound Medicine ER -