RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model

Abstract Background Despite proven therapeutic effects in inflammatory conditions, the specific mechanisms of phytochemical therapies are not well understood. The transcriptome effects of Traumeel (Tr14), a multicomponent natural product, and diclofenac, a non-selective cyclooxygenase (COX) inhibito...

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Autores principales:	Georges St. Laurent, Ian Toma, Bernd Seilheimer, Konstantin Cesnulevicius, Myron Schultz, Michael Tackett, Jianhua Zhou, Maxim Ri, Dmitry Shtokalo, Denis Antonets, Tisha Jepson, Timothy A. McCaffrey
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Inflammation Transcriptome RNA sequencing Traumeel Diclofenac Cyclooxygenase Biotechnology TP248.13-248.65 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/c8303c41583743ea9e38e98bb0993bb8
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spelling	oai:doaj.org-article:c8303c41583743ea9e38e98bb0993bb82021-11-28T12:23:08ZRNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model10.1186/s12864-021-08083-21471-2164https://doaj.org/article/c8303c41583743ea9e38e98bb0993bb82021-11-01T00:00:00Zhttps://doi.org/10.1186/s12864-021-08083-2https://doaj.org/toc/1471-2164Abstract Background Despite proven therapeutic effects in inflammatory conditions, the specific mechanisms of phytochemical therapies are not well understood. The transcriptome effects of Traumeel (Tr14), a multicomponent natural product, and diclofenac, a non-selective cyclooxygenase (COX) inhibitor, were compared in a mouse cutaneous wound healing model to identify both known and novel pathways for the anti-inflammatory effect of plant-derived natural products. Methods Skin samples from abraded mice were analyzed by single-molecule, amplification-free RNAseq transcript profiling at 7 points between 12 and 192 h after injury. Immediately after injury, the wounds were treated with either diclofenac, Tr14, or placebo control (n = 7 per group/time). RNAseq levels were compared between treatment and control at each time point using a systems biology approach. Results At early time points (12–36 h), both control and Tr14-treated wounds showed marked increase in the inducible COX2 enzyme mRNA, while diclofenac-treated wounds did not. Tr14, in contrast, modulated lipoxygenase transcripts, especially ALOX12/15, and phospholipases involved in arachidonate metabolism. Notably, Tr14 modulated a group of cell-type specific markers, including the T cell receptor, that could be explained by an overarching effect on the type of cells that were recruited into the wound tissue. Conclusions Tr14 and diclofenac had very different effects on the COX/LOX synthetic pathway after cutaneous wounding. Tr14 allowed normal autoinduction of COX2 mRNA, but suppressed mRNA levels for key enzymes in the leukotriene synthetic pathway. Tr14 appeared to have a broad ‘phytocellular’ effect on the wound transcriptome by altering the balance of cell types present in the wound.Georges St. LaurentIan TomaBernd SeilheimerKonstantin CesnuleviciusMyron SchultzMichael TackettJianhua ZhouMaxim RiDmitry ShtokaloDenis AntonetsTisha JepsonTimothy A. McCaffreyBMCarticleInflammationTranscriptomeRNA sequencingTraumeelDiclofenacCyclooxygenaseBiotechnologyTP248.13-248.65GeneticsQH426-470ENBMC Genomics, Vol 22, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Inflammation Transcriptome RNA sequencing Traumeel Diclofenac Cyclooxygenase Biotechnology TP248.13-248.65 Genetics QH426-470
spellingShingle	Inflammation Transcriptome RNA sequencing Traumeel Diclofenac Cyclooxygenase Biotechnology TP248.13-248.65 Genetics QH426-470 Georges St. Laurent Ian Toma Bernd Seilheimer Konstantin Cesnulevicius Myron Schultz Michael Tackett Jianhua Zhou Maxim Ri Dmitry Shtokalo Denis Antonets Tisha Jepson Timothy A. McCaffrey RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model
description	Abstract Background Despite proven therapeutic effects in inflammatory conditions, the specific mechanisms of phytochemical therapies are not well understood. The transcriptome effects of Traumeel (Tr14), a multicomponent natural product, and diclofenac, a non-selective cyclooxygenase (COX) inhibitor, were compared in a mouse cutaneous wound healing model to identify both known and novel pathways for the anti-inflammatory effect of plant-derived natural products. Methods Skin samples from abraded mice were analyzed by single-molecule, amplification-free RNAseq transcript profiling at 7 points between 12 and 192 h after injury. Immediately after injury, the wounds were treated with either diclofenac, Tr14, or placebo control (n = 7 per group/time). RNAseq levels were compared between treatment and control at each time point using a systems biology approach. Results At early time points (12–36 h), both control and Tr14-treated wounds showed marked increase in the inducible COX2 enzyme mRNA, while diclofenac-treated wounds did not. Tr14, in contrast, modulated lipoxygenase transcripts, especially ALOX12/15, and phospholipases involved in arachidonate metabolism. Notably, Tr14 modulated a group of cell-type specific markers, including the T cell receptor, that could be explained by an overarching effect on the type of cells that were recruited into the wound tissue. Conclusions Tr14 and diclofenac had very different effects on the COX/LOX synthetic pathway after cutaneous wounding. Tr14 allowed normal autoinduction of COX2 mRNA, but suppressed mRNA levels for key enzymes in the leukotriene synthetic pathway. Tr14 appeared to have a broad ‘phytocellular’ effect on the wound transcriptome by altering the balance of cell types present in the wound.
format	article
author	Georges St. Laurent Ian Toma Bernd Seilheimer Konstantin Cesnulevicius Myron Schultz Michael Tackett Jianhua Zhou Maxim Ri Dmitry Shtokalo Denis Antonets Tisha Jepson Timothy A. McCaffrey
author_facet	Georges St. Laurent Ian Toma Bernd Seilheimer Konstantin Cesnulevicius Myron Schultz Michael Tackett Jianhua Zhou Maxim Ri Dmitry Shtokalo Denis Antonets Tisha Jepson Timothy A. McCaffrey
author_sort	Georges St. Laurent
title	RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model
title_short	RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model
title_full	RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model
title_fullStr	RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model
title_full_unstemmed	RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model
title_sort	rnaseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model
publisher	BMC
publishDate	2021
url	https://doaj.org/article/c8303c41583743ea9e38e98bb0993bb8
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RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model

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