Upregulation of equine matrix metalloproteinase 1 by bovine papillomavirus type 1 is through the transcription factor activator protein-1.
Abstract: Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type 1 (BPV-1) activity is necessary for the transformation phenotype of equine fibroblasts. Among the many changes induced by BPV-1, matrix metalloproteinase 1 (MMP-1) upregulation contributes to the invasiveness of equine fibroblasts. However, it is not yet known how BPV-1 proteins regulate equine MMP-1 expression. To elucidate this mechanism, the equine MMP-1 promoter was cloned and analysed. A putative activator protein-1 (AP-1)-binding site was demonstrated to be crucial for upregulated MMP-1 promoter activity by BPV-1. BPV-1 E6 and E7 proteins increased MMP-1 promoter activity, and inhibition of BPV-1 gene expression by small interfering RNA significantly reduced the promoter activity. c-Jun and Fra-1, two components of the AP-1 transcription factor complex, were overexpressed and activated by BPV-1 in equine fibroblasts. Finally, BPV-1 E5, E6 and E7 proteins increased MMP-1 mRNA and protein expression. In conclusion, the expression of MMP-1 can be enhanced by BPV-1 oncoproteins E6 and E7 through the AP-1 transcription factor and by E5 via an indirect mechanism. These findings shed light on the mechanism of BPV-1-mediated equine fibroblast infiltration and indicate that both BPV-1 oncoproteins and AP-1 could be potential targets for equine sarcoid therapy.
Publication Date: 2011-07-20 PubMed ID: 21775582DOI: 10.1099/vir.0.033431-0Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research investigates how equine skin tumors, specifically equine sarcoids, are shaped by the Bovine papillomavirus type 1 (BPV-1). The researchers found out that the BPV-1 virus, through various proteins, increases the expression of matrix metalloproteinase 1 (MMP-1), a fact that encourages the invasion and infiltration of these tumors.
Understanding the Terminology
- Equine sarcoids: These are common skin tumors in horses and other related species.
- Equine fibroblasts: These are cells that produce the structural framework (collagen and extracellular matrix) for animal tissues.
- Matrix metalloproteinase 1 (MMP-1): An enzyme that breaks down the extracellular matrix, a process that contributes to the progression of diseases like cancer.
- Bovine papillomavirus type 1 (BPV-1): A virus seen in cows that can also impact equids; it is associated with skin tumors in these species.
Role of BPV-1 in Equine Skin Tumors
- The research indicates that the BPV-1 activity is necessary for the invasive transformation of equine fibroblasts, which leads to skin tumors.
- The major impact of BPV-1 is the upregulation or increase in the production of MMP-1, which further instigates the invasiveness of the fibroblasts.
- How the BPV-1 virus regulates the MMP-1 expression wasn’t previously known, which made this study necessary.
The Role of Activator Protein-1 and E-Proteins
- The researchers identified that activated protein-1 (AP-1), a transcription factor, was crucial for increasing MMP-1 activity.
- Among BPV-1 proteins, E6 and E7 were found to increase MMP-1 activity. Conversely, blocking these proteins led to a reduction of MMP-1 activity.
- c-Jun and Fra-1, two components of AP-1, were overexpressed and activated in presence of BPV-1, indicating a close association between BPV-1 and AP-1.
- BPV-1 E5, E6, and E7 proteins all increased MMP-1 mRNA and protein expression. Specifically, E6 and E7 did this through AP-1, while E5 did this indirectly.
Implications and Future Directions
- Understanding the role of BPV-1 and AP-1 in causing equine sarcoids could lead to new therapeutic approaches by targeting these agents.
- By inhibiting the activity of BPV-1 or the AP-1 transcription factor, the invasiveness of these tumors could potentially be controlled.
Cite This Article
APA
Yuan Z, Gault EA, Campo MS, Nasir L.
(2011).
Upregulation of equine matrix metalloproteinase 1 by bovine papillomavirus type 1 is through the transcription factor activator protein-1.
J Gen Virol, 92(Pt 11), 2608-2619.
https://doi.org/10.1099/vir.0.033431-0 Publication
Researcher Affiliations
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
MeSH Terms
- Animals
- Binding Sites
- Bovine papillomavirus 1 / pathogenicity
- Cell Line
- Gene Expression Profiling
- Horses
- Host-Pathogen Interactions
- Matrix Metalloproteinase 1 / biosynthesis
- Oncogene Proteins, Viral / metabolism
- Promoter Regions, Genetic
- Transcription Factor AP-1 / metabolism
- Up-Regulation
Grant Funding
- Cancer Research UK
Citations
This article has been cited 4 times.- Daraban Bocaneti F, Altamura G, Corteggio A, Tanase OI, Dascalu MA, Pasca SA, Hritcu O, Mares M, Borzacchiello G. Expression of collagenases (matrix metalloproteinase-1, -8, -13) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in naturally occurring bovine cutaneous fibropapillomas.. Front Vet Sci 2022;9:1072672.
- Corteggio A, Altamura G, Roperto F, Borzacchiello G. Bovine papillomavirus E5 and E7 oncoproteins in naturally occurring tumors: are two better than one?. Infect Agent Cancer 2013 Jan 9;8(1):1.
- Finlay M, Yuan Z, Morgan IM, Campo MS, Nasir L. Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53.. Vet Res 2012 Dec 4;43(1):81.
- Strazzullo M, Corteggio A, Altamura G, Francioso R, Roperto F, D'Esposito M, Borzacchiello G. Molecular and epigenetic analysis of the fragile histidine triad tumour suppressor gene in equine sarcoids.. BMC Vet Res 2012 Mar 16;8:30.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
