Expression of matrix metalloproteinases (MMPs)-2/-7/-9/-14 and tissue inhibitors of MMPs (TIMPs)-1/-2 in bovine cutaneous fibropapillomas associated with BPV-2 infection.
Abstract: Bovine papillomaviruses -1/-2 (BPVs) are small non-enveloped double-stranded DNA viruses able to infect the skin of bovids and equids, causing development of neoplastic lesions such as bovine cutaneous fibropapillomas and equine sarcoid. Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases that degrade basal membrane and extracellular matrix, whose function is essential in physiological processes such as tissue remodeling and wound healing. MMPs activity is finely regulated by a balancing with expression of tissue inhibitors of MMPs (TIMPs), a process that is impaired during tumour development. BPV infection is associated with upregulation of MMPs and /or their unbalancing with TIMPs, contributing to local invasion and impairment of extracellular matrix remodeling in equine sarcoid; however, studies regarding this topic in bovine fibropapillomas are lacking. Unassigned: The aim of this study was to perform an immunohistochemical and biochemical analysis on a panel of MMPs and TIMPs in BPV-2 positive bovine cutaneous fibropapillomas vs. normal skin samples. Unassigned: Immunohistochemistry revealed a cytoplasmic expression of MMP-2 (15/19), a cytoplasmic and perinuclear immunoreactivity of MMP-7 (19/19) and MMP-9 (19/19), along with a cytoplasmic and nuclear pattern of MMP-14 (16/19), accompanied by a cytoplasmic expression of TIMP-1 (14/19) and TIMP-2 (18/19) in tumour samples; western blotting revealed an overexpression of MMP-2 (8/9), MMP-7 (9/9) and MMP-9 (9/9), and a decreased level of MMP-14 (9/9), TIMP-1 (9/9) and TIMP-2 (9/9) in tumour versus normal skin samples. Moreover, gelatine zymography confirmed the expression of pro-active MMP-2 (9/9) and MMP-9 (9/9) and, most importantly, indicated the presence and increased activity of their active forms (82 and 62 kDa, respectively) in tumour samples. Unassigned: This is the first study describing MMPs and TIMPs in bovine cutaneous fibropapillomas and our results suggest that their unbalanced expression in presence of BPV-2 may play a significant role in tumour development. A further analysis of supplementary MMPs and TIMPs could bring new important insights into the papillomavirus induced tumours.
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The research focuses on the occurrence and interplay of certain proteins called matrix metalloproteinases and their inhibitors in growths on cow skin connected to two strains of bovine papillomavirus. The study suggests that an imbalance in these protein levels could be a key factor in the development of these tumors.
Background
The two strains of bovine papillomavirus (BPVs), BPV-1 and BPV-2, are known to infect the skin of bovids and equids, leading to growths or tumors.
Matrix metalloproteinases (MMPs) are proteins that help with tissue remodeling and wound healing by breaking down the structures that make up our tissues.
The activity of these MMPs is regulated by other proteins called tissue inhibitors of MMPs (TIMPs), and imbalances in the levels of these proteins can lead to disease development.
Prior research has suggested that a BPV infection can disrupt the balance of these proteins, but the specifics of this in the context of bovine skin tumors has not been studied in depth before.
Methodology
The primary goal of this study was to identify and analyse the expressions of specific MMPs and TIMPs in skin samples with BPV-2 positive bovine cutaneous fibropapillomas (skin tumors).
They used a technique known as immunohistochemistry (a method to visually detect the presence of specific proteins in a tissue) on the samples collected.
They also used western blotting, a method for detecting specific proteins, and gelatine zymography, a technique used to detect and quantify enzymatic activity of MMPs.
Findings and Interpretations
Immunohistochemistry revealed evidence of several MMPs and TIMPs present in the skin tumor samples.
Additionally, the use of western blotting revealed higher levels of MMP-2, MMP-7 and MMP-9 and lower levels of MMP-14, TIMP-1 and TIMP-2 in the tumor samples compared to normal skin samples.
Gelatine zymography confirmed the presence and increased activity of MMP-2 and MMP-9 in the tumor samples. This implies that the presence and imbalance of MMPs and TIMPs in the presence of BPV-2 play a significant role in the development of the skin tumors in bovines.
Implications and Future Research
This being the first study to describe the occurrences of MMPs and TIMPs in bovine cutaneous fibropapillomas, it adds significant knowledge to the understanding of the molecular mechanisms underlying the tumor development in these BPV-2 infections.
If further analysis of additional MMPs and TIMPs could be carried out, this could lead to even deeper insights into this kind of tumor development induced by papillomavirus.
Cite This Article
APA
Daraban Bocaneti F, Altamura G, Corteggio A, Tanase OI, Dascalu MA, Pasca SA, Hritcu O, Mares M, Borzacchiello G.
(2022).
Expression of matrix metalloproteinases (MMPs)-2/-7/-9/-14 and tissue inhibitors of MMPs (TIMPs)-1/-2 in bovine cutaneous fibropapillomas associated with BPV-2 infection.
Front Vet Sci, 9, 1063580.
https://doi.org/10.3389/fvets.2022.1063580
Department of Public Health, Faculty of Veterinary Medicine, Iasi University of Life Sciences "Ion Ionescu de la Brad", Iaşi, Romania.
Altamura, Gennaro
Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", Naples, Italy.
Corteggio, Annunziata
Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Naples, Italy.
Tanase, Oana Irina
Department of Public Health, Faculty of Veterinary Medicine, Iasi University of Life Sciences "Ion Ionescu de la Brad", Iaşi, Romania.
Dascalu, Mihaela Anca
Department of Public Health, Faculty of Veterinary Medicine, Iasi University of Life Sciences "Ion Ionescu de la Brad", Iaşi, Romania.
Pasca, Sorin Aurelian
Department of Pathology, Faculty of Veterinary Medicine, Iasi University of Life Sciences "Ion Ionescu de la Brad", Iaşi, Romania.
Hritcu, Ozana
Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", Naples, Italy.
Mares, Mihai
Department of Public Health, Faculty of Veterinary Medicine, Iasi University of Life Sciences "Ion Ionescu de la Brad", Iaşi, Romania.
Borzacchiello, Giuseppe
Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", Naples, Italy.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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