Evaluation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in Equine Sarcoid: An Immunohistochemical and Biochemical Study

Martano, Manuela; Altamura, Gennaro; Power, Karen A.; Restucci, Brunella; Carella, Francesca; Borzacchiello, Giuseppe; Maiolino, Paola

doi:10.3390/pathogens9010058

Cited by 5 publications

(10 citation statements)

References 73 publications

(109 reference statements)

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“…This is why we aimed at establishing a hypoxia-induced control for the immunofluorescent experiments. To our knowledge, this is not described for equine cultures to date even though there are reports on mainly intracytoplasmic HIF-1α expression in other equine tissues [ 37 , 38 ] and sarcoids as well as keratinocyte cultures [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Development of a constant pressure perfused ex vivo model of the equine larynx

et al. 2021

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Distal axonopathy is seen in a broad range of species including equine patients. In horses, this degenerative disorder of the recurrent laryngeal nerve is described as recurrent laryngeal neuropathy (RLN). The dysfunctional innervation of the cricoarytenoideus dorsalis muscle (CAD) leads to a loss of performance in affected horses. In general, ex vivo models of the larynx are rare and for equine patients, just one short report is available. To allow for testing new therapy approaches in an isolated organ model, we examined equine larynges in a constant pressure perfused setup. In order to check the vitality and functionality of the isolated larynx, the vessels´ reaction to norepinephrine (NE) and sodium nitroprusside (NP) as vasoactive agents was tested. Additionally, the contractility of the CAD was checked via electrical stimulation. To determine the extent of hypoxic alterations, lactate dehydrogenase (LDH) and lactate were measured and an immunofluorescent analysis of hypoxia-inducible factor (HIF-1α), a key transcription factor in hypoxia, was performed. For this, a hypoxia-induced cell culture for HIF-1α was developed. The application of NE led to an expected vasoconstriction while NP caused the expected vasodilation. During a perfusion period of 352 ±20.78 min, LDH values were in the reference range and lactate values slightly exceeded the reference range at the end of the perfusion. HIF-1α nuclear translocation could reliably be detected in the hypoxia-induced cell cultures, but not in sections of the perfused CAD. With the approach presented here, a solid basis for perfusing equine larynges was established and may serve as a tool for further investigations of equine larynx disorders as well as a transferrable model for other species.

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Section: Discussionmentioning

confidence: 99%

Development of a constant pressure perfused ex vivo model of the equine larynx

et al. 2021

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“…Furthermore, Martano et al 50 have observed an increase of HIF‐1α expression in equine sarcoids; this mediator plays a key role in oxygen homeostasis 51 . Available literature confirms that VEGF expression is mediated by HIF‐1α during hypoxia, and the expression of HIF‐1α directly correlates with VEGF expression and tumour vascularity in several tumour types 50 . Based on these results, it has been hypothesised that BPV could have a relevant role in HIF‐1α pathway regulation, contributing to the development of equine sarcoids by promoting HIF‐1α/VEGF‐mediated tumour angiogenesis 50 …”

Section: Changes In Gene Expression In Equine Sarcoid Tissuementioning

confidence: 99%

“…As a consequence, in equine sarcoids, VEGF may be involved not only in angiogenesis, but also in ECM homeostasis maintenance and remodelling 24 . Furthermore, Martano et al 50 have observed an increase of HIF‐1α expression in equine sarcoids; this mediator plays a key role in oxygen homeostasis 51 . Available literature confirms that VEGF expression is mediated by HIF‐1α during hypoxia, and the expression of HIF‐1α directly correlates with VEGF expression and tumour vascularity in several tumour types 50 .…”

Section: Changes In Gene Expression In Equine Sarcoid Tissuementioning

confidence: 99%

Molecular approaches to equine sarcoids

Semik-Gurgul

2020

Equine Veterinary Journal

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Sarcoids are the most commonly diagnosed skin tumours in equines. Bovine papillomaviruses (BPVs) are the primary causative agent of sarcoids. There has been intensive research to discover the molecular mechanisms that may contribute to the aetiopathogenesis of this disease and tumour suppressors and proto‐oncogenes known to play a role in human neoplastic conditions have been investigated in equine sarcoids. Current approaches include the identification of gene expression profiles, characterising sarcoid and normal skin tissues, and an assessment of epigenetic alterations such as microRNA differential expression and DNA methylation status. This review focuses on selected groups of genes that contribute to the molecular mechanisms of sarcoid formation. These genes have the potential to complement current clinical examinations of equine sarcoid disease in diagnosis, prognosis, therapeutic response and screening.

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“…95 On the other hand, the development of equine sarcoid is associated with an elevated level of the transcription factor hypoxia-inducible factor-1 alpha (HIF-1α). 64 This transcription factor is activated in response to hypoxia and leads to angiogenesis, the development of new vessels necessary for neoplastic invasion, growth, and metastasis.…”

Section: Molecular Featuresmentioning

confidence: 99%

Equine Sarcoids—Causes, Molecular Changes, and Clinicopathologic Features: A Review

et al. 2021

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Equine sarcoid is the most common skin tumor of horses. Clinically, it occurs as a locally invasive, fibroblastic, wart-like lesion of equine skin, which has 6 clinical classes: occult, verrucose, nodular, fibroblastic, mixed, and malignant. Sarcoids may be single but multiple lesions are more frequent. The typical histological feature is increased density of dermal fibroblasts which form interlacing bundles and whorls within the dermis. Lesions are mostly persistent, resist therapy, and tend to recur following treatment. In general, sarcoids are not fatal but their location, size, and progression to the more aggressive form may lead to the withdrawal of a horse from use and serious infringement of their welfare leading to the loss of valuable animals. Bovine papillomavirus (BPV) type 1 and less commonly type 2 contribute to the development of equine sarcoid. The viral genome and proteins are detected in a high percentage of cases. Furthermore, viral oncoprotein activity leads to changes in the fibroblastic tissue similar to changes seen in other types of tumors. Equine sarcoids are characterized by a loss of tumor suppressor activity and changes allowing abnormal formation of the affected tissue, as well as y immune defense abnormalities that weaken the host’s immune response. This impaired immune response to BPV infection appears to be crucial for the development of lesions that do not spontaneously regress, as occurs in BPV-infected cows.

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Evaluation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in Equine Sarcoid: An Immunohistochemical and Biochemical Study

Cited by 5 publications

References 73 publications

Development of a constant pressure perfused ex vivo model of the equine larynx

Development of a constant pressure perfused ex vivo model of the equine larynx

Molecular approaches to equine sarcoids

Equine Sarcoids—Causes, Molecular Changes, and Clinicopathologic Features: A Review

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