Abstract
Delayed wound healing is a major complication associated with diabetes and is a result of a complex interplay among diverse deregulated cellular parameters. Although several genes and pathways have been identified to be mediating impaired wound closure, the role of microRNAs (miRNAs) in these events is not very well understood. Here, we identify an altered miRNA signature in the prolonged inflammatory phase in a wound during diabetes, with increased infiltration of inflammatory cells in the basal layer of the epidermis. Nineteen miRNAs were downregulated in diabetic rat wounds (as compared with normal rat wound, d 7 postwounding) together with inhibited levels of the central miRNA biosynthesis enzyme, Dicer, suggesting that in wounds of diabetic rats, the decreased levels of Dicer are presumably responsible for miRNA downregulation. Compared with unwounded skin, Dicer levels were significantly upregulated 12 d postwounding in normal rats, and this result was notably absent in diabetic rats that showed impaired wound closure. In a wound-healing specific quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) array, 10 genes were significantly altered in the diabetic rat wound and included growth factors and collagens. Network analyses demonstrated significant interactions and correlations between the miRNA predicted targets (regulators) and the 10 wound-healing specific genes, suggesting altered miRNAs might fine-tune the levels of these genes that determine wound closure. Dicer inhibition prevented HaCaT cell migration and affected wound closure. Altered levels of Dicer and miRNAs are critical during delayed wound closure and offer promising targets to address the issue of impaired wound healing.
Highlights
Wound healing is a complex biological process involving an intricate crosstalk of cellular events including inflammation, reepithelialization and restoration of affected tissues [1,2]
Wound healing during diabetes is characterized by a prolonged inflammatory phase that interferes with the timely initiation of subsequent phases, thereby delaying wound closure
We evaluated the status of inflammation in the normal and diabetic rat skin wounded tissue on d 7 postwounding
Summary
Wound healing is a complex biological process involving an intricate crosstalk of cellular events including inflammation, reepithelialization and restoration of affected tissues [1,2]. Invasion of neutrophils into the wound area primarily removes the resident microbes, and this step is followed by active movement of macrophages and monocytes that act to remove dead tissues and other debris materials [3,4]. These phenomena involve the generation of reactive oxygen species and nitric oxide, and these inflammatory events are followed closely by reepithelialization that is achieved by migration and proliferation of keratinocytes and fibroblasts in and around the wound site. Basement membrane proteins orderly reappear and epidermal cells tend to get attached to the basement membrane and dermis followed by formation of granulation tissue [1,5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
