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

BMC Genomics

Denis Antonets¹  Ian Toma²  Timothy A. McCaffrey²  Bernd Seilheimer³  Konstantin Cesnulevicius³  Myron Schultz³  Jianhua Zhou⁴  Maxim Ri⁵  Dmitry Shtokalo⁶  Georges St. Laurent⁷  Michael Tackett⁷  Tisha Jepson⁷ 

[1] AcademGene, LLC, Novosibirsk, Russia;A.P. Ershov Institute of Informatics Systems, Novosibirsk, Russia;Department of Medicine, Division of Genomic Medicine, The George Washington University Medical Center, 2300 Eye St, 20037, Washington D.C, USA;Heel GmbH, Baden-Baden, Germany;The St. Laurent Institute, Vancouver, WA, USA;The St. Laurent Institute, Vancouver, WA, USA;AcademGene, LLC, Novosibirsk, Russia;The St. Laurent Institute, Vancouver, WA, USA;AcademGene, LLC, Novosibirsk, Russia;A.P. Ershov Institute of Informatics Systems, Novosibirsk, Russia;The St. Laurent Institute, Vancouver, WA, USA;SeqLL, Inc., Woburn, MA, USA;

关键词: Inflammation;    Transcriptome;    RNA sequencing;    Traumeel;    Diclofenac;    Cyclooxygenase;    Lipoxygenase;    Phospholipase;   

DOI  :  10.1186/s12864-021-08083-2

来源: Springer

【 摘 要 】

BackgroundDespite 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.MethodsSkin 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.ResultsAt 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.ConclusionsTr14 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.

【 授权许可】

CC BY