Deep Sequencing Transcriptome Analysis of Murine Wound Healing: Effects of a Multicomponent, Multitarget Natural Product Therapy-Tr14

Abstract

Wound healing involves an orchestrated response that engages multiple processes, such as hemostasis, cellular migration, extracellular matrix synthesis, and in particular, inflammation. Using a murine model of cutaneous wound repair, the transcriptome was mapped from 12 h to 8 days post-injury, and in response to a multicomponent, multi-target natural product, Tr14. Using single-molecule RNA sequencing (RNA-seq), there were clear temporal changes in known transcripts related to wound healing pathways, and additional novel transcripts of both coding and non-coding genes. Tr14 treatment modulated >100 transcripts related to key wound repair pathways, such as response to wounding, wound contraction, and cytokine response. The results provide the most precise and comprehensive characterization to date of the transcriptome's response to skin damage, repair, and multicomponent natural product therapy. By understanding the wound repair process, and the effects of natural products, it should be possible to intervene more effectively in diseases involving aberrant repair.

Lens Epithelial Cells Initiate an Inflammatory Response Following Cataract Surgery

“…While RNA-seq experiments testing the early stages of abrasive wound healing in mouse skin are qualitatively consistent with our results in lens as mRNAs for genes involved in the cytokine response are elevated by 12 hours post wounding, remain quite high at 24 hours post wounding, and generally fall by 36 hours post wounding, none of the six genes that we highlighted for study in LECs (the top three most upregulated plus three others of biological interest) were included in the top 100 changed genes in abrasive skin wounding in mice. 87 Further, the responses appear quite different quantitatively as well. For instance, while CXCL1 (the most elevated gene in LECs PCS) is also elevated after abrasive skin wounding, the response is much more mutated than in LECs while COX-2, whose mRNA is elevated 248-fold in LECs PCS, is not altered in skin post abrasive wounding at any time tested.…”

“…For instance, while CXCL1 (the most elevated gene in LECs PCS) is also elevated after abrasive skin wounding, the response is much more mutated than in LECs while COX-2, whose mRNA is elevated 248-fold in LECs PCS, is not altered in skin post abrasive wounding at any time tested. 87 The diversity of transcriptional responses to wounding is further highlighted by a recent paper demonstrating that human oral mucosa and skin have very different responses to incisional wounding, largely because the naïve oral mucosa already expresses many genes usually associated with inflammation, including S100A8 / A9 (which are among the top upregulated genes in injured lens epithelium, while CXCL1 and CCL2 (other top upregulated genes in injured mouse lens epithelium) do not upregulate after muscosal injury but are upregulated 48 hours and 5 days after incisional wounding of human skin. 88 …”

Skin wound healing triggers epigenetic modifications of histone H4

“…Recent studies have started to profile the wound transcriptome [9][10][11][12]; however, changes in the epigenetic landscape of the epithelial barrier during healing is largely unknown. To this end, we used antibodies capable of identifying the specific acetylation status of histone H4 at lysines K5, K8, K12, and K16 during the process of healing.…”

Bioregulatory drugs in osteoarthritis management

“…Компоненты препарата оказывают влияние на высвобождение макрофагов IL-6, которые играют ведущую роль в развитии хронического воспаления и ангиогенеза [2]. В эксперименте на животных было показано, что терапия препаратом Цель Т индуцированного артроза привела к меньшей эрозии хряща [28], чем в контрольной группе. При этом уровень васкуляризации глубоких слоев хряща был многократно меньше, чем в группе сравнения.…”