MicroRNA-132 with Therapeutic Potential in Chronic Wounds

Abstract

Chronic wounds represent a major and rising health and economic burden worldwide. There is a continued search toward more effective wound therapy. We found significantly reduced microRNA-132 (miR-132) expression in human diabetic ulcers compared with normal skin wounds and also in skin wounds of leptin receptor-deficient (db/db) diabetic mice compared with wild-type mice. Local replenishment of miR-132 in the wounds of db/db mice accelerated wound closure effectively, which was accompanied by increased proliferation of wound edge keratinocytes and reduced inflammation. The pro-healing effect of miR-132 was further supported by global transcriptome analysis, which showed that several inflammation-related signaling pathways (e.g., NF-κB, NOD-like receptor, toll-like receptor, and tumor necrosis factor signaling pathways) were the top ones regulated by miR-132 in vivo. Moreover, we topically applied liposome-formulated miR-132 mimics mixed with pluronic F-127 gel on human ex vivo skin wounds, which promoted re-epithelialization. Together, our study showed the therapeutic potential of miR-132 in chronic wounds, which warrants further evaluation in controlled clinical trials.

microRNA-184 and Its lncRNA Sponge UCA1 are Induced in Wounded Keratinocytes in a Store-Operated Calcium Entry-Dependent Manner

“…From a translational perspective, the ability of exogenous miR-184 to accelerate HPEK migration suggesting miR-184 enhancement may promote re-epithelisation during wound healing. Recently, miR-132 was found to promote closure of diabetic mouse wounds and ex vivo human skin wounds (Li et al, 2017), showcasing the potential of miRNAmediated wound healing. Questions remain though as to which vehicles are likely to support the safest and most efficient delivery of miRNA mimics to patient skin (Ross, 2018) and addressing these issues will catalyse the realisation of miRNA-based therapies to address unmet dermatological needs.…”

“…For instance. miR-21, miR-31 and miR-132 promote keratinocyte migration (Li et al, 2015, Li et al, 2017, Wang et al, 2012, Yang et al, 2011. In contrast, over expression of miR-24 or miR-483-3p inhibited HPEK migration (Amelio et al, 2012, Bertero et al, 2011.…”

Descriptive vs mechanistic scientific approach to study wound healing and its inhibition: Is there a value of translational research involving human subjects?

“…S. aureus induced miR‐15b‐5p, subsequently repressing DNA repair and diminishing inflammatory response, revealing a novel mechanism of healing inhibition in chronic DFU colonized with this pathogen . DFU are also characterized by a significant reduction of miR‐132, which contributes to the deregulation of inflammation‐related pathways such as NF‐κB, NOD‐like receptor, Toll‐like receptor and TNF‐α signalling . Multiple proteomic studies have utilized chronic wound fluid as an accessible source of biomaterial, revealing not only deregulation of secreted host proteases, but also specific peptides from human thrombin derived as result of wound infection .…”

Identification and functional analysis of inflammation‐related miRNAs in skin wound repair

“…Here, molecular networks of inflammation-dependent mRNAs and miRNAs are revealed to provide new insights regarding inflammation and tissue repair machinery. Type II diabetes patients exhibit chronic skin ulcers as a result of delayed skin wound healing and demonstrate an increased incidence of skin infections due to disturbed vascular function (Nunan, Harding, & Martin, 2014 (Icli et al, 2016;Li et al, 2017;Lucas et al, 2017;Pizzino et al, 2018). Moreover, bone marrow-derived angiogenic cell therapy with manipulation by a miR-27b mimic also indirectly accelerated diabetic wound closure .…”