Project description:When compared to skin, oral mucosal wounds heal rapidly and with reduced scar formation. This study used an Affymetrix microarray platform to compare the transcriptomes of oral mucosa and skin wounds in order to identify critical differences in the healing response at these two sites. Using microarrays, we explored the differences in gene expression in skin and oral mucosal wound healing in a murine model of paired equivalent-sized wounds. Samples were examined from day 0 to day 10 and spanned all stages of the wound healing process. Unwounded matched tissue was used as a control. Tissue samples collected at each post-wounding time point, as well as control samples, were represented by 3 biological replicates.
Project description:Skin wound healing is one of the major prevalent medical problems in the worldwide. Wound healing involves multi-process synergy and re-epithelialization is an essential part of wound healing. Histone H3K36 tri-methylase Setd2 has been extensively studied in different biological processes and diseases. However, the function of Setd2 in the wound healing remains unclear. To elucidate the biological role of Setd2 in the skin wound healing, conditional gene targeting was employed to establish epidermis-specific Setd2-deficient mice. We found that Setd2 deficiency resulted in accelerated re-epithelialization during cutaneous wound healing by promoting keratinocytes proliferation and migration. Furthermore, we demonstrated that loss of Setd2 activated the AKT/mTOR pathway, and pharmacological inhibitions of AKT and mTOR with MK2206 and rapamycin delayed wound closure, respectively. In conclusion, our results reveal the essential role of Setd2 in skin wound healing that is Setd2 loss promotes cutaneous wound healing via activation of AKT/mTOR signaling.
Project description:Acomys exhibits a blunted immune response to wounding, and shares characteristics with fetal wound healing We used mouse microarrays to compare gene expression profiles during wound healing between the African spiny mouse (Acomys) and the house mouse (Mus)
Project description:Olfactomedin-4 (OLFM4) is an olfactomedin-domain-containing glycoprotein which regulates cell adhesion, proliferation, gastrointestinal inflammation, innate immunity and cancer metastasis. In the present study investigated its role in skin regeneration and wound healing. We found that OLFM4 expression is transiently upregulated in the proliferative phase of cutaneous wound healing in humans as well as in mice. Moreover, a significant increase in OLFM4 expression was detected in the skin of lesional psoriasis, a chronic inflammatory disease characterized by keratinocyte hyperproliferation. In vitro experiments demonstrated that OLFM4 can selectively stimulate keratinocyte proliferation and increase both keratinocyte and fibroblast migration ability. Using proteotransciptomic pathway analysis we revealed that transcription factors POU5F1/OCT4 and ESR1 acted as hubs for OLFM4-dependent signalling in keratinocytes. In vivo experiments utilizing mouse splinted full-thickness cutaneous wound healing model showed that application of recombinant OLFM4 protein can significantly improve wound healing time. Taken together, our results suggest that OLFM4 is a transiently upregulated inflammatory signal that promotes wound healing by supporting the functions of both dermal and epidermal cell compartments.
Project description:A significant number of pathological conditions, accompanied by chronic non-healing wounds, demands searching for new modern therapeutic approaches. Well-documented ability of O. felineus to initiate extracellular matrix (ECM) remodeling and liver epithelium regeneration suggests that its bioactive molecules may stimulate skin wound healing processes. The aim of this study was to investigate the wound healing potential of the Opisthorchis felineus excretory-secretory and lysate proteins on a murine model. The following methods were used for the study: histological (wounded skin condition), immunohistochemical (ECM, neoangiogenesis, O. felineus GST and TPx proteins), gene expression analysis (inflammation, angiogenesis, ECM condition). O. felineus excretory-secretory product (ESP) and lysate proteins have revealed wound-healing potential, they: i) reduce inflammation levels, ii) modulate vascular response, iii) stimulate collagen deposition and dermal ECM remodeling. Additional proteomic analysis of adult O. felineus ESP and lysate samples was conducted. Proteomic analysis approach called GeLC-MS / MS was chosen to study of the excretory-secretory product and lysate proteins. This approach is based on one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), in-gel protein digestion with trypsin followed by liquid chromatography-tandem mass spectrometry. The SDS-PAGE step allow to removes hemozoin also as detergents, buffers and salts from the protein extract that may interfere with mass spectrometry analysis
Project description:Human and murine skin wounding commonly result in fibrotic scarring but the murine wounding model Wound Induced Hair Neogenesis (WIHN) can frequently result in a regenerative repair response. Here we show in single cell RNA-seq comparisons of semi-regenerative and fibrotic WIHN wounds, increased expression of phagocytic/lysosomal genes in macrophages associated with predominance of fibrotic myofibroblasts in fibrotic wounds. Investigation revealed that macrophages in the late wound drive fibrosis by phagocytizing dermal Wnt inhibitor SFRP4 to establish persistent Wnt activity. In accordance, phagocytosis abrogation resulted in transient Wnt activity and a more regenerative healing. Phagocytosis of SFRP4 was integrin-mediated and dependent on the interaction of SFRP4 with the EDA splice variant of fibronectin. In the human skin condition Hidradenitis suppurativa, phagocytosis of SFRP4 by macrophages correlated with fibrotic wound repair. These results reveal that macrophages can modulate a key signaling pathway via phagocytosis to alter the skin wound healing fate.