MicroRNA Expression in Chronic Venous Leg Ulcers and Implications for Wound Healing: A Scoping Review

Purpose: Chronic venous leg ulcers (CVLUs) comprise the majority of lower-extremity wounds, yet their pathophysiology is not fully understood. While research has shown that microRNAs are an important component of wound inflammation, few have explored the role of microRNAs (miRNAs) in the healing of CVLUs. This scoping review examines miRNAs in CVLUs and the association with wound healing. Methods: In December 2023, we searched MEDLINE/PubMed, Embase, Scopus, and CINAHL for studies published in 2013-2023 examining miRNAs in CVLU healing. Results: Six studies met inclusion criteria. MicroRNAs were extracted from various specimens including serum, skin biopsy samples, and adipose tissue-derived mesenchymal cells from individuals with CVLUs. Overexpression of miR-221, miR-222, miR-92a, and miR-301a-3p hindered angiogenesis, while overexpression of miR-296, miR-126, miR-378, and miR-210 facilitated angiogenesis. Overexpression of miR-34a/c, miR-301a-3p, miR-450-5p, miR-424-5p, miR-516-5p, and miR-7704 increased local inflammatory responses and inhibited keratinocytes proliferation, impairing healing, while overexpression of miR-19a/b and miR-20 downregulated keratinocytes' inflammatory response, promoting healing. Downregulation of miR-205, miR-96-5p, and miR-218-5p enhanced cellular proliferation and promoted wound healing. Downregulation of miR-17-92 was linked with impaired healing. Discussion: MicroRNAs play a role in regulating angiogenesis, inflammatory responses, and cell migration in chronic-wound healing. However, studies of miRNAs in CVLUs are limited and lack a standardized approach to measurement and quantification. Further research is warranted to elucidate the mechanisms underlying microRNA involvement in CVLU healing to better understand the pathophysiology and for the future development of targeted therapies.