Gene expression profile at single cell level of skin cells isolated from db/db mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE253098 | GEO | 2024/01/17
REPOSITORIES: GEO
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Project description:Female sex hormones are beneficial effects for wound healing. However, till date, whether topical estrogen application can promote cutaneous wound healing in diabetes remains unclear. Therefore, the present study aimed to validate the effect of topical estrogen application on cutaneous wound healing in a type 2 diabetes db/db mice model. In total, 22 db/db female mice with type 2 diabetes and eight C57BL/6J female mice were subjected to two full-thickness wound injuries. The mice were divided into the db/db, db/db + estrogen, db/db + vehicle, and wild type (WT) groups. Wound healing was assessed until day 14. The db/db group had a significantly high wound area ratio (wound area/initial wound area) on days 3–14 and a significantly low re-epithelialization ratio on days 7 and 14. Moreover, their angiogenesis ratio was significantly low on day 7 and high on day 14. In contrast, compared with the db/db group, the db/db + estrogen group had a significantly lower wound area ratio on days 1–14 and angiogenesis ratio on day 14, thereby indicating early withdrawal of new blood vessels, as well as a significantly higher re-epithelialization ratio on days 7 and 14 and Ym1+ M2 macrophage/macrophage ratio on day 7. Moreover, microarray analysis showed that the top 10 upregulated or downregulated genes in the db/db group were reversed by estrogen treatment, particularly on day 14, in comparison with the WT group. Thus, topical estrogen application reduced the wound area, promoted re-epithelialization and angiogenesis, and increased the number of M2 macrophages in mice with type 2 diabetes. Furthermore, it improved the differential regulation of genes in db/db mice. Therefore, such treatment can enhance cutaneous wound healing in female mice with type 2 diabetes.
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Project description:MiR-132 is one of the most upregulated miRNAs in human skin wounds at the inflammatory phase of healing. MiR-132 inhibits inflammation but promotes growth of epidermal keratinocytes, indicating that it may facilitate the inflammatory-proliferative phase transition during wound repair. Following this line of research, here we evaluated the therapeutic potential of miR-132 in chronic wound using mouse in vivo wound model. We performed a global transcriptome analysis of skin wounds of leptin receptor-deficient (db/db) mice treated with miR-132 or control mimics. Db/db mouse has been used as a type 2 diabetic model with impaired wound healing capacity.
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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.
2020-12-25 | GSE163860 | GEO
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.
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Project description:Severe angiopathy has been postulated as a major driver for diabetes associated secondary complications. So far the knowledge on underlying mechanisms and thereon based therapeutic options to attenuate these pathologies are limited. Here we systematically administered ABCB5+ MSCs for the treatment of chronic non-healing diabetic wounds employing db/db mice, a type II diabetes model as their number markedly declined during diabetes. We found that administration of ABCB5+ MSCs markedly accelerates wound closure in diabetic db/db mice as opposed to the vehicle treated control group. Strikingly, administration of ABCB5+ MSCs at the edges of the diabetic wounds triggered considerable neoangiogenesis, most likely by the releasing a Ribonuclease angiogenin that was identified through secretome analysis of ABCB5+ MSCs. Interestingly, silencing of angiogenin in ABCB5+ MSCs significantly delayed wound closure in diabetic db/db mice indicating its key role in skin regeneration. Moreover, angiogenin also impacted the polarization of macrophages. The findings from this study will provide novel insight into the unique capacity of ABCB5+ MSCs to mount an adaptive response at the wound site with the delivery of angiogenic molecules holds significant promise for the therapy of non-healing diabetes foot ulcers, and other pathologies with impaired angiogenesis. The benefits for refined stem cell based therapies is virtually unlimited.
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2021-04-08 | GSE171662 | GEO
Project description:Bacterial biofilm infections associated with wounded skin are prevalent, recalcitrant and in urgent need of treatments. Additionally, host responses in the skin to biofilm infections are not well understood. Here we employed a human organoid skin model to explore the transcriptomic changes of thermally-injured epidermis to Methicillin-resistant Staphylococcus aureus (MRSA) biofilm colonization. MRSA biofilm impaired skin barrier function, enhanced extracellular matrix remodelling, elicited inflammatory responses including IL-17, IL-12 family and IL-6 family interleukin signalling and modulated skin metabolism. Synthetic antibiofilm peptide DJK-5 effectively diminished MRSA biofilm associated with wounded human ex vivo skin. In the epidermis, DJK-5 shifted the overall skin transcriptome towards homeostasis including modulating the biofilm induced inflammatory response, promoting the skin DNA repair function, and downregulating MRSA invasion of thermally damaged skin. These data revealed the intrinsic promise of synthetic peptides in treating inflammation and biofilm infections.
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