Journal of Pharmacy and Pharmacology 2 (2014) 104-113 miRNA-146a and miRNA-200b Antagomirs Accelerate Wound Healing through the Regulation of VEGF and Fibronectin Biao Feng 1 , Shali Chen 1 , Linbo Zhang 1, 2 , Yanan Cao 1, 3 and Subrata Chakrabarti 1 1. Department of Pathology, Western University, London N6A 5C1, Ontario, Canada 2. The School of Life Sciences, Jilin Agricultural University, Changchun 130118, Jilin, P.R. China 3. Heilongjiang Key Laboratory of Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang15700, Heilongjiang, P.R. China Received: December 04, 2013 / Accepted: February 07, 2014 / Published: February 28, 2014. Abstract: miRNAs play important roles in the post-transcriptional regulation of most transcripts and control several biological processes. We have shown that miR-200b regulates VEGF and miR-146a regulates ECM (extracellular matrix) protein, FN (fibronectin) production. We examined the effects of these two miRNAs in wound healing in vitro and in animals with or without diabetes. Microvascular ECs (endothelial cells) with or without miR inhibitor (antagomir) transfection were tested for VEGF and FN production. Scratch assays and angiogenesis assays were performed. Wounds in the back of mice with or without streptozotocin-induced diabetes were treated with antagomirs alone or in combinations. The wounds were measured and tissues were examined for mRNAs, proteins and miRNAs and examined histologically. In the ECs, miR-200b or miR-146a inhibitors increased VEGF and FN production, cell migration and tube formation. Wound healing in the animals, along with increased production of specific proteins were accelerated by miR-200b or miR-146a inhibitor treatment and was pronounced when these two were combined. In diabetes, although delayed, similar patterns were seen. These results indicated that combination of miR-146a and miR-200b inhibitor treatment is useful in wound healing both in normal and in diabetic conditions. miRNA mediated wound healing may potentially constitute a novel therapeutic approach. Key words: miR-200b, miR-146a, wound healing, vascular endothelial growth factor, fibronectin. 1. Introduction Wound healing remains a significant clinical problem. In particular, non-healing chronic skin wounds are a common and severe complication of diabetes and are associated with significant morbidity [1]. Wound healing is impaired in the diabetic population due to impaired circulation and increased susceptibility to infections [2]. From the mechanistic standpoint, angiogenesis and increased ECM (extracellular matrix) protein production are key Corresponding author: Subrata Chakrabarti, Ph.D., professor, research field: diabetic complications. E-mail: Subrata.Chakrabarti@lhsc.on.ca. factors for successful wound healing [3]. It has been shown that such process can be stimulated by external delivery of growth factors [3]. MicroRNAs (miRNAs) are gaining attentions in several biologic processes as they play major roles in gene regulation. These conserved ~20-25 nucleotide long RNA molecules are produced from specific genes. They are controlled by tissue specific regulation and negatively regulate gene expression at the post-transcriptional level by binding to the 3’ UTR (untranslated region) of specific mRNAs [4]. Several miRNAs have been found in the skin and are thought to play a crucial role in a wide range of biologic DAVID PUBLISHING D