Assessment of BPV-1 Mediated Matrix Metalloproteinase Genes Deregulation in the In Vivo and In Vitro Models Designed to Explore Molecular Nature of Equine Sarcoids.
Abstract: Matrix metalloproteinases (s) represent a family of enzymes capable of biocatalytically breaking down the structural and functional proteins responsible for extracellular matrix (ECM) integrity. This capability is widely used in physiological processes; however, imbalanced MMP activity can trigger the onset and progression of various pathological changes, including the neoplasmic transformation of different cell types. We sought to uncover molecular mechanisms underlying alterations in transcriptional profiles of genes coding for s, which were comprehensively identified in equine adult dermal tissue bioptates, sarcoid-derived explants, and ex vivo expanded adult cutaneous fibroblast cell (ACFC) lines subjected to inducible oncogenic transformation into sarcoid-like cells. The results strongly support the hypothesis that the transcriptional activity of genes correlates with molecular modifications arising in equine dermal cells during their conversion into sarcoid cells. The alterations in transcription signatures occurs in both sarcoid tissues and experimentally transformed equine ACFC lines expressing transgene, which were characterized by gene up- and down-regulation patterns.
Publication Date: 2022-04-08 PubMed ID: 35455948PubMed Central: PMC9025493DOI: 10.3390/cells11081268Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the role of genes coding for matrix metalloproteinase enzymes in the development of equine sarcoids, a type of tumor in horses, using both in vivo and in vitro models.
Understanding Matrix Metalloproteinases and Their Impact on Equine Sarcoids
- Matrix metalloproteinases (MMPs) are enzymes that play a critical role in maintaining the structural integrity of extracellular matrix (ECM) – the non-cellular component present within all tissues and organs that provides essential support to cells.
- In normal conditions, these enzymes help to maintain the health and functionality of tissues and organs. however, when their activity becomes imbalanced, it may lead to various pathological changes including the formation of tumors or neoplasms.
The Research Hypothesis and Objectives
- The researchers hypothesized that changes in the transcriptional activity of the genes coding for matrix metalloproteinases correlate with the molecular alterations occurring in horse skin cells during their conversion into sarcoid cells.
- The goal was to find the underlying molecular causes of these alteration using models crafted from adult equine dermal tissues, sarcoid-derived explants, and cutaneous fibroblast cells manipulated to mimic the transformation into sarcoid cells.
Findings and Implications
- The results strongly supported the hypothesis. There were apparent changes in the transcription activity of the MMP genes both in the sarcoid tissues and in the experimentally manipulated fibroblast cell lines.
- These changes were characterized by patterns of up- and down-regulation of gene expression, implying that the activity of MMPs was much disrupted in the sarcoid cells.
- This means MMPs could have a significant role in the formation and progression of equine sarcoids – a critical insight that should be considered in the development of future therapies for this condition.
Cite This Article
APA
Podstawski P, Ropka-Molik K, Semik-Gurgul E, Samiec M, Skrzyszowska M, Podstawski Z, Szmatoła T, Witkowski M, Pawlina-Tyszko K.
(2022).
Assessment of BPV-1 Mediated Matrix Metalloproteinase Genes Deregulation in the In Vivo and In Vitro Models Designed to Explore Molecular Nature of Equine Sarcoids.
Cells, 11(8), 1268.
https://doi.org/10.3390/cells11081268 Publication
Researcher Affiliations
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, 32-083 Balice, Poland.
- Department of Animal Reproduction, Anatomy and Genomics, University of Agriculture in Kraków, Mickiewicza 24/28, 30-059 Krakow, Poland.
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, 32-083 Balice, Poland.
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, 32-083 Balice, Poland.
- Department of Reproductive Biotechnology and Cryoconservation, National Research Institute of Animal Production, Krakowska 1 Street, 32-083 Balice, Poland.
- Department of Reproductive Biotechnology and Cryoconservation, National Research Institute of Animal Production, Krakowska 1 Street, 32-083 Balice, Poland.
- Department of Animal Reproduction, Anatomy and Genomics, University of Agriculture in Kraków, Mickiewicza 24/28, 30-059 Krakow, Poland.
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, 32-083 Balice, Poland.
- Center for Experimental and Innovative Medicine, University of Agriculture in Krakow, Rędzina 1c Street, 30-248 Krakow, Poland.
- Institute of Veterinary Medicine, University Centre of Veterinary Medicine JU-AU, Mickiewicza 24/28, 30-248 Krakow, Poland.
- Szpital Koni Służewiec, Puławska 266, 02-684 Warszawa, Poland.
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, 32-083 Balice, Poland.
MeSH Terms
- Animals
- Cell Transformation, Neoplastic
- Horse Diseases / genetics
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Matrix Metalloproteinases / genetics
- Sarcoidosis
- Skin / pathology
- Skin Diseases
- Skin Neoplasms / pathology
Conflict of Interest Statement
The authors declare no conflict of interest.
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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.
- Daraban Bocaneti F, Altamura G, Corteggio A, Tanase OI, Dascalu MA, Pasca SA, Hritcu O, Mares M, Borzacchiello G. 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 2022;9:1063580.
- Podstawski P, Ropka-Molik K, Semik-Gurgul E, Samiec M, Skrzyszowska M, Podstawski Z, Szmatoła T, Witkowski M, Pawlina-Tyszko K. Tracking the Molecular Scenarios for Tumorigenic Remodeling of Extracellular Matrix Based on Gene Expression Profiling in Equine Skin Neoplasia Models. Int J Mol Sci 2022 Jun 10;23(12).
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