PMID- 36518899 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221221 IS - 2297-1769 (Print) IS - 2297-1769 (Electronic) IS - 2297-1769 (Linking) VI - 9 DP - 2022 TI - 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. PG - 1063580 LID - 10.3389/fvets.2022.1063580 [doi] LID - 1063580 AB - INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CI - Copyright (c) 2022 Daraban Bocaneti, Altamura, Corteggio, Tanase, Dascalu, Pasca, Hritcu, Mares and Borzacchiello. FAU - Daraban Bocaneti, Florentina AU - Daraban Bocaneti F AD - Department of Public Health, Faculty of Veterinary Medicine, Iasi University of Life Sciences "Ion Ionescu de la Brad", Iasi, Romania. FAU - Altamura, Gennaro AU - Altamura G AD - Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", Naples, Italy. FAU - Corteggio, Annunziata AU - Corteggio A AD - Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Naples, Italy. FAU - Tanase, Oana Irina AU - Tanase OI AD - Department of Public Health, Faculty of Veterinary Medicine, Iasi University of Life Sciences "Ion Ionescu de la Brad", Iasi, Romania. FAU - Dascalu, Mihaela Anca AU - Dascalu MA AD - Department of Public Health, Faculty of Veterinary Medicine, Iasi University of Life Sciences "Ion Ionescu de la Brad", Iasi, Romania. FAU - Pasca, Sorin Aurelian AU - Pasca SA AD - Department of Pathology, Faculty of Veterinary Medicine, Iasi University of Life Sciences "Ion Ionescu de la Brad", Iasi, Romania. FAU - Hritcu, Ozana AU - Hritcu O AD - Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", Naples, Italy. FAU - Mares, Mihai AU - Mares M AD - Department of Public Health, Faculty of Veterinary Medicine, Iasi University of Life Sciences "Ion Ionescu de la Brad", Iasi, Romania. FAU - Borzacchiello, Giuseppe AU - Borzacchiello G AD - Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", Naples, Italy. LA - eng PT - Journal Article DEP - 20221128 PL - Switzerland TA - Front Vet Sci JT - Frontiers in veterinary science JID - 101666658 PMC - PMC9744227 OTO - NOTNLM OT - BPV OT - MMP OT - TIMP OT - bovine fibropapilloma OT - tumor invasion COIS- 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. EDAT- 2022/12/16 06:00 MHDA- 2022/12/16 06:01 PMCR- 2022/01/01 CRDT- 2022/12/15 02:32 PHST- 2022/10/07 00:00 [received] PHST- 2022/11/04 00:00 [accepted] PHST- 2022/12/15 02:32 [entrez] PHST- 2022/12/16 06:00 [pubmed] PHST- 2022/12/16 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fvets.2022.1063580 [doi] PST - epublish SO - Front Vet Sci. 2022 Nov 28;9:1063580. doi: 10.3389/fvets.2022.1063580. eCollection 2022.