Background Anti-inflammatory agents are used widely in treating numerous inflammatory conditions. The effect of Tr14, a multitargeted natural product, was compared to diclofenac, a non-selective cyclooxygenase inhibitor, on cutaneous wound repair in mice.
Objectives To compare the effect of diclofenac with Tr14 on the transcriptome after cutaneous wounding in the mouse.
Methods After abrasive wounding, the wounds were treated with topical Tr14 or diclofenac at clinically relevant doses. An additional group received subcutaneous Tr14 injections. The healing wounds were analyzed for RNA transcript profiling by RNAseq at specific times (12h, 24h, 36h, 72h, 96h, 120h, 196h) after injury. Differentially expressed genes (DEGs) were computed at each time point between diclofenac vs control or Tr14 vs control using EdgeR.
Results Across time points, Tr14 treatment modulated a number of transcripts related to key wound repair pathways such as cellular differentiation, wound contraction, and cell mobility. Diclofenac, in contrast, changed gene expression mainly in two areas: Prominent effects were observed with regard to DNA chromatin regulation and ribosomal function, further effects were observed on the prostaglandin pathway and wound repair factors. In many of the key pathways modulated by Tr14, such as the defense response and cell motility, diclofenac tended to have an opposite effect on gene expression. At 12 hours post-injury, there were 521 transcripts significantly elevated and 1027 transcripts that were decreased by diclofenac treatment. By comparison, using a similar number of transcripts altered by Tr14 treatment, only 4 transcripts were increased in common, and 5 transcripts were decreased in common, suggesting that the therapies have different effects on the transcriptome.
Conclusions The overall patterns of the Tr14 and diclofenac responses in the transcriptome during wound repair are very different. The Tr14 effect is most pronounced on the defense response, cell motility, and anti-apoptotic pathways. In contrast, diclofenac mainly affected histones and chromatin remodeling systems, as well as ribosomal systems that would be expected to alter the translational pattern of diclofenac-treated cells.
Disclosure of Interest G. St. Laurent, III: None declared, B. Seilheimer: None declared, M. Tackett: None declared, J. Zhou: None declared, D. Shtokalo: None declared, Y. Vyatkin: None declared, P. Kapranov: None declared, I. Toma: None declared, T. Mccaffrey Speakers bureau: TM has received speaker's honorarium from HEEL, GmbH