Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds

Abstract Argonaute 2 bound mature microRNA (Ago2‐miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation‐related Ago2‐miRNAs (miR‐139‐5p, miR‐142‐3p, miR‐142‐5p, and miR‐223) and show that miR‐223 is critical for infection control. miR‐223Y/− mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin‐6 expression, and markedly improved repair of Staphylococcus aureus‐infected wounds. We also showed that the expression of miR‐223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR‐223Y/−‐derived neutrophils, or miR‐223 antisense oligodeoxynucleotides in S. aureus‐infected wild‐type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR‐223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR‐223 might be of therapeutic benefit for infected wounds in the clinic

Dynamic movement and turnover of extracellular matrices during tissue development and maintenance.

Extracellular matrices (ECMs) are essential for the architecture and function of animal tissues. ECMs have been thought to be highly stable structures; however, too much stability of ECMs would hamper tissue remodelling required for organ development and maintenance. Regarding this conundrum, this article reviews multiple lines of evidence that ECMs are in fact rapidly moving and replacing components in diverse organisms including hydra, worms, flies, and vertebrates. Also discussed are how cells behave on/in such dynamic ECMs, how ECM dynamics contributes to embryogenesis and adult tissue homoeostasis, and what molecular mechanisms exist behind the dynamics. In addition, it is highlighted how cutting-edge technologies such as genome engineering, live imaging, and mathematical modelling have contributed to reveal the previously invisible dynamics of ECMs. The idea that ECMs are unchanging is to be changed, and ECM dynamics is emerging as a hitherto unrecognized critical factor for tissue development and maintenance

Mechanical waves help zebrafish regrow their tails

Regenerative animals accurately regrow lost appendages. Now, research suggests that mechanical waves propagating from the amputation edge have a key role in this process

Analysis of the molecular mechanisms of re-epithelialization in Drosophila embryos

Significance: The epidermis provides the main barrier function of skin, and therefore its repair following wounding is an essential component of wound healing. Repair of the epidermis, also known as reepithelialization, occurs by collective migration of epithelial cells from around the wound edge across the wound until the advancing edges meet and fuse. Therapeutic manipulation of this process could potentially be used to accelerate wound healing. Recent Advances: It is difficult to analyze the cellular and molecular mechanisms of reepithelialization in human tissue, so a variety of model organisms have been used to improve our understanding of the process. One model system that has been especially useful is the embryo of the fruit fly Drosophila, which provides a simple, accessible model of the epidermis and can be manipulated genetically, allowing detailed analysis of reepithelialization at the molecular level. This review will highlight the key insights that have been gained from studying reepithelialization in Drosophila embryos. Critical Issues: Slow reepithelialization increases the risk of wounds becoming infected and ulcerous; therefore, the development of therapies to accelerate or enhance the process would be a great clinical advance. Improving our understanding of the molecular mechanisms that underlie reepithelialization will help in the development of such therapies. Future Directions: Research in Drosophila embryos has identified a variety of genes and proteins involved in triggering and driving reepithelialization, many of which are conserved in humans. These novel reepithelialization proteins are potential therapeutic targets and therefore findings obtained in Drosophila may ultimately lead to significant clinical advances

A New Interactive Visualization System with Force Feedback Device in 3-D Electromagnetics

This paper describes an interactive visualization system with force feedback device in three-dimensional (3-D) electromagnetics. We present an extension and improvement of the previously developed two-dimensional (2-D) interactive visualization system used for visualization of various 2-D field distribution maps with arbitrarily movable objects inside the analyzed region. We improve our 2-D visualization system to deal with real 3-D models. Moreover, we knew that perceiving electromagnetic force along with observing various 3-D field distribution maps could significantly help users to better understand the complex electromagnetic phenomenon. Driven by these ideas, we have developed a 3-D interactive visualization system with force feedback device for fast and easy perception of the electromagnetic force and electromagnetic field distribution maps for 3-D models with movable object

Endocytosis-dependent co-ordination of multiple actin regulators is required for wound healing

The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form “signaling centers” along the wound edge that control actin assembly. We conclude that coordination of actin assembly, AJ remodeling, and membrane traffic is required for the construction of a motile leading edge during wound healing