Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy

Chemotherapy-induced neuropathy (CIN) is a major adverse effect associated with many chemotherapeutics, including bortezomib (BTZ). Several mechanisms are involved in CIN, and recently a role has been proposed for prokineticins (PKs), a chemokine family that induces proinflammatory/pro-algogen media...

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Autores principales:	Laura Rullo, Silvia Franchi, Giada Amodeo, Francesca Felicia Caputi, Benedetta Verduci, Loredana Maria Losapio, Paola Sacerdote, Patrizia Romualdi, Sanzio Candeletti
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	KDM6A PC1 prokineticins PPARα PPARγ bortezomib Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/55688ea8a4034eddb51f8dd6b4699591
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spelling	oai:doaj.org-article:55688ea8a4034eddb51f8dd6b46995912021-11-11T17:19:56ZInterplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy10.3390/ijms2221119131422-00671661-6596https://doaj.org/article/55688ea8a4034eddb51f8dd6b46995912021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11913https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Chemotherapy-induced neuropathy (CIN) is a major adverse effect associated with many chemotherapeutics, including bortezomib (BTZ). Several mechanisms are involved in CIN, and recently a role has been proposed for prokineticins (PKs), a chemokine family that induces proinflammatory/pro-algogen mediator release and drives the epigenetic control of genes involved in cellular differentiation. The present study evaluated the relationships between epigenetic mechanisms and PKs in a mice model of BTZ-induced painful neuropathy. To this end, spinal cord alterations of histone demethylase KDM6A, nuclear receptors PPARα/PPARγ, PK2, and pro-inflammatory cytokines IL-6 and IL-1β were assessed in neuropathic mice treated with the PK receptors (PKRs) antagonist PC1. BTZ treatment promoted a precocious upregulation of KDM6A, PPARs, and IL-6, and a delayed increase of PK2 and IL-1β. PC1 counteracted allodynia and prevented the increase of PK2 and of IL-1β in BTZ neuropathic mice. The blockade of PKRs signaling also opposed to KDM6A increase and induced an upregulation of PPAR gene transcription. These data showed the involvement of epigenetic modulatory enzymes in spinal tissue phenomena associated with BTZ painful neuropathy and underline a role of PKs in sustaining the increase of proinflammatory cytokines and in exerting an inhibitory control on the expression of PPARs through the regulation of KDM6A gene expression in the spinal cord.Laura RulloSilvia FranchiGiada AmodeoFrancesca Felicia CaputiBenedetta VerduciLoredana Maria LosapioPaola SacerdotePatrizia RomualdiSanzio CandelettiMDPI AGarticleKDM6APC1prokineticinsPPARαPPARγbortezomibBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11913, p 11913 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	KDM6A PC1 prokineticins PPARα PPARγ bortezomib Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	KDM6A PC1 prokineticins PPARα PPARγ bortezomib Biology (General) QH301-705.5 Chemistry QD1-999 Laura Rullo Silvia Franchi Giada Amodeo Francesca Felicia Caputi Benedetta Verduci Loredana Maria Losapio Paola Sacerdote Patrizia Romualdi Sanzio Candeletti Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy
description	Chemotherapy-induced neuropathy (CIN) is a major adverse effect associated with many chemotherapeutics, including bortezomib (BTZ). Several mechanisms are involved in CIN, and recently a role has been proposed for prokineticins (PKs), a chemokine family that induces proinflammatory/pro-algogen mediator release and drives the epigenetic control of genes involved in cellular differentiation. The present study evaluated the relationships between epigenetic mechanisms and PKs in a mice model of BTZ-induced painful neuropathy. To this end, spinal cord alterations of histone demethylase KDM6A, nuclear receptors PPARα/PPARγ, PK2, and pro-inflammatory cytokines IL-6 and IL-1β were assessed in neuropathic mice treated with the PK receptors (PKRs) antagonist PC1. BTZ treatment promoted a precocious upregulation of KDM6A, PPARs, and IL-6, and a delayed increase of PK2 and IL-1β. PC1 counteracted allodynia and prevented the increase of PK2 and of IL-1β in BTZ neuropathic mice. The blockade of PKRs signaling also opposed to KDM6A increase and induced an upregulation of PPAR gene transcription. These data showed the involvement of epigenetic modulatory enzymes in spinal tissue phenomena associated with BTZ painful neuropathy and underline a role of PKs in sustaining the increase of proinflammatory cytokines and in exerting an inhibitory control on the expression of PPARs through the regulation of KDM6A gene expression in the spinal cord.
format	article
author	Laura Rullo Silvia Franchi Giada Amodeo Francesca Felicia Caputi Benedetta Verduci Loredana Maria Losapio Paola Sacerdote Patrizia Romualdi Sanzio Candeletti
author_facet	Laura Rullo Silvia Franchi Giada Amodeo Francesca Felicia Caputi Benedetta Verduci Loredana Maria Losapio Paola Sacerdote Patrizia Romualdi Sanzio Candeletti
author_sort	Laura Rullo
title	Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy
title_short	Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy
title_full	Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy
title_fullStr	Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy
title_full_unstemmed	Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy
title_sort	interplay between prokineticins and histone demethylase kdm6a in a murine model of bortezomib-induced neuropathy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/55688ea8a4034eddb51f8dd6b4699591
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Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy

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