scholarly journals Imunofan—RDKVYR Peptide—Stimulates Skin Cell Proliferation and Promotes Tissue Repair

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2884
Author(s):  
Justyna Sawicka ◽  
Maria Dzierżyńska ◽  
Anna Wardowska ◽  
Milena Deptuła ◽  
Piotr Rogujski ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Dna Demethylation ◽  
Transcriptional Responses ◽  
Skin Cell ◽  
Active Dna Demethylation ◽  
Potential Efficacy ◽  
Keratinocyte Cell ◽  
Synthetic Hexapeptide ◽  
Vast Range

Regeneration and wound healing are vital to tissue homeostasis and organism survival. One of the biggest challenges of today’s science and medicine is finding methods and factors to stimulate these processes in the human body. Effective solutions to promote regenerative responses will accelerate advances in tissue engineering, regenerative medicine, transplantology, and a number of other clinical specialties. In this study, we assessed the potential efficacy of a synthetic hexapeptide, RDKVYR, for the stimulation of tissue repair and wound healing. The hexapeptide is marketed under the name “Imunofan” (IM) as an immunostimulant. IM displayed stability in aqueous solutions, while in plasma it was rapidly bound by albumins. Structural analyses demonstrated the conformational flexibility of the peptide. Tests in human fibroblast and keratinocyte cell lines showed that IM exerted a statistically significant (p < 0.05) pro-proliferative activity (30–40% and 20–50% increase in proliferation of fibroblast and keratinocytes, respectively), revealed no cytotoxicity over a vast range of concentrations (p < 0.05), and had no allergic properties. IM was found to induce significant transcriptional responses, such as enhanced activity of genes involved in active DNA demethylation (p < 0.05) in fibroblasts and activation of genes involved in immune responses, migration, and chemotaxis in adipose-derived stem cells derived from surgery donors. Experiments in a model of ear pinna injury in mice indicated that IM moderately promoted tissue repair (8% in BALB/c and 36% in C57BL/6 in comparison to control).

scholarly journals TET2-interacting long noncoding RNA promotes active DNA demethylation of the MMP-9 promoter in diabetic wound healing

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Liyan Zhou ◽  
Meng Ren ◽  
Tingting Zeng ◽  
Wei Wang ◽  
Xiaoyi Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Excision Repair ◽  
Skin Wound ◽  
Dna Demethylation ◽  
Skin Wound Healing ◽  
Active Dna Demethylation ◽  
Diabetic Wound Healing ◽  
Base Excision

Abstract Wound healing in diabetic skin is impaired by excessive activation of matrix metalloproteinase-9 (MMP-9). MMP-9 transcription is activated by Ten-eleven translocation 2 (TET2), a well-known DNA demethylation protein that induces MMP-9 promoter demethylation in diabetic skin tissues. However, how TET2 is targeted to specific loci in the MMP-9 promoter is unknown. Here, we identified a TET2-interacting long noncoding RNA (TETILA) that is upregulated in human diabetic skin tissues. TETILA regulates TET2 subcellular localization and enzymatic activity, indirectly activating MMP-9 promoter demethylation. TETILA also recruits thymine-DNA glycosylase (TDG), which simultaneously interacts with TET2, for base excision repair-mediated MMP-9 promoter demethylation. Together, our results suggest that the TETILA serves as a genomic homing signal for TET2-mediated demethylation specific loci in MMP-9 promoter, thereby disrupting the process of diabetic skin wound healing.

scholarly journals Positioning of nucleosomes containing γ-H2AX precedes active DNA demethylation and transcription initiation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stephanie Dobersch ◽  
Karla Rubio ◽  
Indrabahadur Singh ◽  
Stefan Günther ◽  
Johannes Graumann ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
High Mobility ◽  
Dna Demethylation ◽  
High Mobility Group ◽  
Regulation Of Transcription ◽  
Dna Breaks ◽  
Transcriptional Initiation ◽  
High Mobility Group Proteins ◽  
Active Dna Demethylation ◽  
Repair Mechanisms

AbstractIn addition to nucleosomes, chromatin contains non-histone chromatin-associated proteins, of which the high-mobility group proteins are the most abundant. Chromatin-mediated regulation of transcription involves DNA methylation and histone modifications. However, the order of events and the precise function of high-mobility group proteins during transcription initiation remain unclear. Here we show that high-mobility group AT-hook 2 protein (HMGA2) induces DNA nicks at the transcription start site, which are required by the histone chaperone FACT complex to incorporate nucleosomes containing the histone variant H2A.X. Further, phosphorylation of H2A.X at S139 (γ-H2AX) is required for repair-mediated DNA demethylation and transcription activation. The relevance of these findings is demonstrated within the context of TGFB1 signaling and idiopathic pulmonary fibrosis, suggesting therapies against this lethal disease. Our data support the concept that chromatin opening during transcriptional initiation involves intermediates with DNA breaks that subsequently require DNA repair mechanisms to ensure genome integrity.

scholarly journals Gene specific-loci quantitative and single-base resolution analysis of 5-formylcytosine by compound-mediated polymerase chain reaction

2018 ◽  
Vol 9 (15) ◽  
pp. 3723-3728 ◽  
Author(s):  
Yafen Wang ◽  
Chaoxing Liu ◽  
Xiong Zhang ◽  
Wei Yang ◽  
Fan Wu ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Dna Demethylation ◽  
Chain Reaction ◽  
Single Base ◽  
Active Dna Demethylation ◽  
Key Players ◽  
Resolution Analysis ◽  
Single Base Resolution ◽  
Polymerase Chain

5-Formylcytosine (5fC) is known as one of the key players in the process of active DNA demethylation and displays essential epigenetic functions in mammals.

scholarly journals Methyl-CpG-Binding Domain Protein MBD7 Is Required for Active DNA Demethylation in Arabidopsis

2015 ◽  
Vol 167 (3) ◽  
pp. 905-914 ◽  
Author(s):  
Chunlei Wang ◽  
Xiaomei Dong ◽  
Dan Jin ◽  
Yusheng Zhao ◽  
Shaojun Xie ◽  
...  
Keyword(s):  
Dna Demethylation ◽  
Binding Domain ◽  
Active Dna Demethylation ◽  
Domain Protein

Solid emulsion gel as a vehicle for delivery of polyunsaturated fatty acids: implications for tissue repair, dermal angiogenesis and wound healing

2008 ◽  
Vol 2 (7) ◽  
pp. 383-393 ◽  
Author(s):  
Kirill I. Shingel ◽  
Marie-Pierre Faure ◽  
Laurent Azoulay ◽  
Christophe Roberge ◽  
Richard J. Deckelbaum
Keyword(s):  
Fatty Acids ◽  
Wound Healing ◽  
Polyunsaturated Fatty Acids ◽  
Tissue Repair ◽  
Emulsion Gel

scholarly journals Squalene Stimulates a Key Innate Immune Cell to Foster Wound Healing and Tissue Repair

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Cristina Sánchez-Quesada ◽  
Alicia López-Biedma ◽  
Estefania Toledo ◽  
José J. Gaforio
Keyword(s):  
Wound Healing ◽  
Inflammatory Cytokines ◽  
Tissue Repair ◽  
Immune Cell ◽  
Critical Role ◽  
Virgin Olive Oil ◽  
Skin Damage ◽  
Macrophage Response ◽  
Anti Inflammatory ◽  
Minor Compounds

Anti-inflammatory effects of virgin olive oil (VOO) have been described recently, along with its wound healing effect. One of the main minor compounds found in VOO is squalene (SQ), which also possesses preventive effects against skin damage and anti-inflammatory properties. The inflammatory response is involved in wound healing and manages the whole process by macrophages, among others, as the main innate cells with a critical role in the promotion and resolution of inflammation for tissue repair. Because of that, this work is claimed to describe the role that squalene exerts in the immunomodulation of M1 proinflammatory macrophages, which are the first cells implicate in recent injuries. Pro- and anti-inflammatory cytokines were analysed using TPH1 cell experimental model. SQ induced an increase in the synthesis of anti-inflammatory cytokines, such as IL-10, IL-13, and IL-4, and a decrease in proinflammatory signals, such as TNF-α and NF-κB in M1 proinflammatory macrophages. Furthermore, SQ enhanced remodelling and repairing signals (TIMP-2) and recruitment signals of eosinophils and neutrophils, responsible for phagocytosis processes. These results suggest that SQ is able to promote wound healing by driving macrophage response in inflammation. Therefore, squalene could be useful at the resolution stage of wound healing.

scholarly journals SUMOylation coordinates BERosome assembly in active DNA demethylation during cell differentiation

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Roland Steinacher ◽  
Zeinab Barekati ◽  
Petar Botev ◽  
Anna Kuśnierczyk ◽  
Geir Slupphaug ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Dna Demethylation ◽  
Active Dna Demethylation
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