Roles of MicroRNA-21 in Skin Wound Healing: A Comprehensive Review

Abstract

MicroRNA-21 (miR-21), one of the early mammalian miRNAs identified, has been detected to be upregulated in multiple biological processes. Increasing evidence has demonstrated the potential values of miR-21 in cutaneous damage and skin wound healing, but lack of a review article to summarize the current evidence on this issue. Based on this review, relevant studies demonstrated that miR-21 played an essential role in wound healing by constituting a complex network with its targeted genes (i.e., PTEN, RECK. SPRY1/2, NF-κB, and TIMP3) and the cascaded signaling pathways (i.e., MAPK/ERK, PI3K/Akt, Wnt/β-catenin/MMP-7, and TGF-β/Smad7-Smad2/3). The treatment effectiveness developed by miR-21 might be associated with the promotion of the fibroblast differentiation, the improvement of angiogenesis, anti-inflammatory, enhancement of the collagen synthesis, and the re-epithelialization of the wound. Currently, miRNA nanocarrier systems have been developed, supporting the feasibility clinical feasibility of such miR-21-based therapy. After further investigations, miR-21 may serve as a potential therapeutic target for wound healing.

Expression of Selected miRNAs in Normal and Cancer-Associated Fibroblasts and in BxPc3 and MIA PaCa-2 Cell Lines of Pancreatic Ductal Adenocarcinoma

“…Predominantly, miR-21 can control various functions of fibroblasts, such as extracellular matrix production, angiogenesis, and inflammation control. This can be particularly important during wound healing and cancer progression [ 30 ]. This striking similarity is not surprising, because wound healing and the cancer microenvironment exhibit many similarities at the cellular and molecular levels [ 31 , 32 ].…”

An Effective Peptide-Based Platform for Efficient Exosomal Loading and Cellular Delivery of a microRNA

“…The major advancements in wound healing include stem cell transplantation, exploiting tissue engineering, implementation of exosomes, and the use of miRNAs in tissue regeneration . miRNA-21-5p has been reported to be a crucial regulator of fibroblast differentiation and angiogenesis, the resolution of inflammation, collagen synthesis, re-epithelialization, cell migration and invasion, and apoptosis − and improves both the rate and quality of wound healing via the BMP, Smad7-Smad2/3-elastin, TGF-β, MAPK/ERK, PI3K/Akt, and Wnt/β-catenin/MMP-7 signaling pathways. Accordingly, we loaded YARA-miRNA-21-5p into UC-MSC-derived exosomes and subsequently investigated if the loaded exosomes had positive effects on one or more aspects of wound healing.…”

“…In this study, we developed a simple peptide-based technology for miRNA loading into exosomes secreted from different mammalian cells, including MSCs, without genetic modification of the parent cells. Here, miRNA-21-5p, a mammalian microRNA known to regulate fibroblast differentiation, angiogenesis, and apoptosis, − was selected to be the model miRNA. To determine the functionality of our loading technology, we then assessed the impact of the loaded exosomes in wound healing assays.…”

Selective Ablation of BCL11A in Epidermal Keratinocytes Alters Skin Homeostasis and Accelerates Excisional Wound Healing In Vivo

“…Additional studies are necessary to determine whether a compensatory upregulation observed in BCL11B expression in absence of BCL11A is a contributor towards the accelerated healing phenotype. Furthermore, noncoding RNAs such as microRNAs (miRNA) and long noncoding RNAs (lncRNA) have received significant attention recently, owing to their rapidly emerging role in modulating nearly every stage of a healing cascade [75][76][77][78][79]. The characterization of expression of noncoding RNAs in the Bcl11a ep−/− mutant skin might provide additional cues about its mechanistic role in facilitating healing.…”