scholarly journals 793. A New In Vivo Human Skin Wound Healing Model: Applications in Cutaneous Gene Therapy

2003 ◽  
Vol 7 (5) ◽  
pp. S306
2020 ◽  
Author(s):  
Delong Ge ◽  
Xiaoxiao Mou ◽  
Liying Liu ◽  
Yanwei Li ◽  
Hui Jiang ◽  
...  

Abstract Background: Interleukin 1 beta (IL-1β) is considered to be a mediator of infectious, inflammatory and autoimmune diseases, and the kinetics of its production is relevant to understanding the pathogenesis of these diseases. Lysophosphatidic acid (LPA), the structurally simplest bioactive phospholipid, is necessary for homeostasis in various physiological and pathophysiological processes and plays a pivotal role in wound healing. Skin trauma can not only weaken the barrier function, but also cause pain and infection. Chronic wounds are characterized by impaired healing and uncontrolled inflammation that damages the protection of the immune system. The aim of this study is to investigate whether inflammatory factor IL-1β has an effect on LPA in the wound healing model. Results: In this study, the kinetics of IL-1β gene expression was studied in vivo and in vitro with a wound healing model by quantitative real-time polymerase chain reaction (qRT-PCR) through LPA treatment. As a result, we found that LPA up-regulated inflammatory factor IL-1β in HaCaT cell and skin wound healing. The pro-inflammatory cytokines IL-1β mRNA had higher expression in LPA-treated mice group 3 days after the treatment. In vitro, after the treatment with LPA (20 μM) for 6, 12, and 24 hours, IL-1β mRNA expression increased by 61.16%, 129.39%, and 117.07%, respectively. Conclusion: These results strongly suggest that IL-1β may regulate LPA-accelerated skin wound healing. IL-1β has significant efficacy, and our observations are of interest to the development of drugs targeting LPA in skin therapy.


BIO-PROTOCOL ◽  
2015 ◽  
Vol 5 (22) ◽  
Author(s):  
Camila Moreira ◽  
Puebla Cassini-Vieira ◽  
Mariana da Silva ◽  
Luc�ola da Barcelos

2015 ◽  
Vol 47 (3) ◽  
pp. 257-265 ◽  
Author(s):  
Yvonne Marquardt ◽  
Philipp M. Amann ◽  
Ruth Heise ◽  
Katharina Czaja ◽  
Timm Steiner ◽  
...  

2011 ◽  
Vol 113 (1) ◽  
pp. 100-109 ◽  
Author(s):  
Rita Negrão ◽  
Raquel Costa ◽  
Delfim Duarte ◽  
Tiago Taveira Gomes ◽  
Pedro Coelho ◽  
...  

2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  

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.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kareem Abdelsaid ◽  
Sudhahar Varadarajan ◽  
Archita Das ◽  
Yutao Liu ◽  
Xuexiu Fang ◽  
...  

Background: Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) have detrimental effects. Exercise not only improves endothelial dysfunction and angiogenesis in T2DM but also induces secretion of exosomes into circulation. Extracellular superoxide dismutase (ecSOD) is a major secretory Cu containing antioxidant enzyme that catalyzes dismutation of O 2 •- to H 2 O 2 and its full activity requires Cu transporter ATP7A. We reported that ecSOD-derived H 2 O 2 in endothelial cells (ECs) enhances angiogenesis while impaired ATP7A-ecSOD axis in diabetes induces endothelial dysfunction. Here we examined whether exercise-derived exosomes (Exe-Exo) may have pro-angiogenic effects via regulating ATP7A-ecSOD axis in T2DM. Results: Two weeks of voluntary wheel exercise of control C57Bl6 mice increased plasma exosome levels (6.2-fold) characterized by Nanosight, TEM and exosome markers (CD63, CD81, Tsg101). Treatment of HUVECs with equal number of exosomes revealed that angiogenic responses such as EC migration (1.8-fold) and tube formation (1.7-fold) were significantly enhanced by Exe-Exo compared to sedentary-derived exosomes (Sed-Exo). This was associated with increased ATP7A (2.9-fold) and ecSOD (1.4-fold) expression in Exe-Exo. Sed-Exo from high fat-induced T2DM mice significantly decreased EC migration (40%) and tube formation (10%) as well as ATP7A expression (28%) compared to Sed-Exo from control mice, which were restored by T2DM Exe-Exo, but not by T2DM/ecSOD KO Exe-Exo. Furthermore, exosomes overexpressing ecSOD (ecSOD-Exo) which mimic exercise increased angiogenesis and H2O2 levels in ECs, which were inhibited by overexpression of catalase. In vivo, skin wound healing model showed that direct application of T2DM Sed-Exo delayed while T2DM Exe-Exo enhanced wound healing of control mice. Furthermore, defective wound healing in T2DM mice or ecSOD KO mice were rescued by ecSOD-Exo application. Conclusion: Exercise training improves pro-angiogenic function of circulating exosomes in T2DM via increasing ATP7A-ecSOD axis, which may provide an effective therapy for promoting angiogenesis and wound repair in metabolic and cardiovascular diseases.


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