scholarly journals Impaired skin wound healing in peroxisome proliferator–activated receptor (PPAR)α and PPARβ mutant mice

2001 ◽  
Vol 154 (4) ◽  
pp. 799-814 ◽  
Author(s):  
Liliane Michalik ◽  
Béatrice Desvergne ◽  
Nguan Soon Tan ◽  
Sharmila Basu-Modak ◽  
Pascal Escher ◽  
...  
Keyword(s):  
Wound Healing ◽  
Skin Wound ◽  
Mutant Mice ◽  
Peroxisome Proliferator ◽  
Skin Wound Healing ◽  
Peroxisome Proliferator Activated Receptor ◽  
Keratinocyte Proliferation ◽  
Tetradecanoylphorbol Acetate ◽  
Proliferation And Differentiation ◽  
And Migration

We show here that the α, β, and γ isotypes of peroxisome proliferator–activated receptor (PPAR) are expressed in the mouse epidermis during fetal development and that they disappear progressively from the interfollicular epithelium after birth. Interestingly, PPARα and β expression is reactivated in the adult epidermis after various stimuli, resulting in keratinocyte proliferation and differentiation such as tetradecanoylphorbol acetate topical application, hair plucking, or skin wound healing. Using PPARα, β, and γ mutant mice, we demonstrate that PPARα and β are important for the rapid epithelialization of a skin wound and that each of them plays a specific role in this process. PPARα is mainly involved in the early inflammation phase of the healing, whereas PPARβ is implicated in the control of keratinocyte proliferation. In addition and very interestingly, PPARβ mutant primary keratinocytes show impaired adhesion and migration properties. Thus, the findings presented here reveal unpredicted roles for PPARα and β in adult mouse epidermal repair.

scholarly journals Regulation of epithelial–mesenchymal IL-1 signaling by PPARβ/δ is essential for skin homeostasis and wound healing

2009 ◽  
Vol 184 (6) ◽  
pp. 817-831 ◽  
Author(s):  
Han Chung Chong ◽  
Ming Jie Tan ◽  
Virginie Philippe ◽  
Siew Hwey Tan ◽  
Chek Kun Tan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Interleukin 1 ◽  
Dermal Fibroblasts ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Keratinocyte Proliferation ◽  
Proliferation And Differentiation ◽  
Keratinocyte Cell ◽  
Normal Human ◽  
Skin Morphogenesis

Skin morphogenesis, maintenance, and healing after wounding require complex epithelial–mesenchymal interactions. In this study, we show that for skin homeostasis, interleukin-1 (IL-1) produced by keratinocytes activates peroxisome proliferator–activated receptor β/δ (PPARβ/δ) expression in underlying fibroblasts, which in turn inhibits the mitotic activity of keratinocytes via inhibition of the IL-1 signaling pathway. In fact, PPARβ/δ stimulates production of the secreted IL-1 receptor antagonist, which leads to an autocrine decrease in IL-1 signaling pathways and consequently decreases production of secreted mitogenic factors by the fibroblasts. This fibroblast PPARβ/δ regulation of the IL-1 signaling is required for proper wound healing and can regulate tumor as well as normal human keratinocyte cell proliferation. Together, these findings provide evidence for a novel homeostatic control of keratinocyte proliferation and differentiation mediated via PPARβ/δ regulation in dermal fibroblasts of IL-1 signaling. Given the ubiquitous expression of PPARβ/δ, other epithelial–mesenchymal interactions may also be regulated in a similar manner.

scholarly journals MicroRNA-31 Promotes Skin Wound Healing by Enhancing Keratinocyte Proliferation and Migration

2015 ◽  
Vol 135 (6) ◽  
pp. 1676-1685 ◽  
Author(s):  
Dongqing Li ◽  
X.I. Li ◽  
Aoxue Wang ◽  
Florian Meisgen ◽  
Andor Pivarcsi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Keratinocyte Proliferation ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals MicroRNA-485-5p reduces keratinocyte proliferation and migration by regulating ITGA5 expression in skin wound healing

2021 ◽  
Vol 19 (12) ◽  
pp. 2553-2557
Author(s):  
Keyu Yuan ◽  
Yi Sun ◽  
Yu Ji
Keyword(s):  
Wound Healing ◽  
Cell Viability ◽  
Skin Wound ◽  
Hacat Cells ◽  
Skin Wound Healing ◽  
Keratinocyte Proliferation ◽  
Downstream Target ◽  
And Migration ◽  
Tgf Β1 ◽  
Proliferation And Migration

Purpose: To determine the effect of miR-485-5p on keratinocyte proliferation and migration.Methods: Human primary keratinocytes (HaCaT cells) were treated with different concentrations of transforming growth factor-β1 (TGF)-β1. miR-485-5p expression levels were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MTT (3-[4,5-dimethylthiazol-2- yl]-2,5 diphenyl tetrazolium bromide) and wound healing assays were performed to investigate the regulatory effects of miR-485-5p on cell viability and migration of HaCaT cells. Downstream target gene expression of miR-485-5p was determined using a luciferase activity assay.Results: In HaCaT cells, miR-485-5p was time- and dose-dependently downregulated by TGF-β1 treatment (p < 0.05). Forced expression of miR-485-5p decreased cell viability and migration of HaCaT cells (p < 0.05). Knockdown of miR-485-5p enhanced HaCaT cell viability and migration. Integrin subunit alpha-5 (ITGA5) was predicted and verified to be a downstream target of miR-485-5p in HaCaT cells. Overexpression of ITGA5 attenuated the miR-485-5p-induced decrease of HaCaT cell viability and migration (p < 0.05).Conclusion: MiR-485-5p reduces cell proliferation and migration of keratinocytes through the regulation of ITGA5. This mechanism provides a potential therapeutic strategy for skin wound healing. Keywords: ITGA5, Keratinocyte, Cell migration, MiR-485-5p, Cell proliferation, Wound healing

scholarly journals Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Wound Closure ◽  
Expression Patterns ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Specific Expression ◽  
Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

scholarly journals The Effect of a Polyester Nanofibrous Membrane with a Fibrin-Platelet Lysate Coating on Keratinocytes and Endothelial Cells in a Co-Culture System

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 457
Author(s):  
Andreu Blanquer ◽  
Jana Musilkova ◽  
Elena Filova ◽  
Johanka Taborska ◽  
Eduard Brynda ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Chronic Wounds ◽  
Human Keratinocytes ◽  
Skin Wound ◽  
Platelet Lysate ◽  
Therapeutic Approaches ◽  
Skin Wound Healing ◽  
New Therapeutic Approaches ◽  
Proliferation And Differentiation

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.

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