MicroRNA-mediated MMP Regulation: Current Diagnostic and Therapeutic Strategies for Metabolic Syndrome

Introduction: Metabolic Syndrome (MS) is a global socioeconomic problem rapidly progressing in accordance with increasing Body Mass Index (BMI) and age. It is a consortium of risk factors, such as dyslipidaemia, insulin resistance, leptin resistance, reduced adiponectin, glucose intolerance, hyperglycemia, and hypertension. Collectively, these factors accelerate the onset of type 2 diabetes mellitus, cardiovascular disease, stroke, and certain cancers such as breast, liver pancreatic, and colon cancer. Extracellular Matrix (ECM) and basement membrane remodeling play a central role during pathogenesis of MS as they regulate diverse cell functions including proliferation, differentiation, and migration. Therefore, regulation of proteins that remodel the ECM offers promising therapeutic opportunities for most of the MS. Matrix Metalloproteinases (MMPs), a family of zinc dependent endopeptidases, are the main enzymes involved in ECM remodeling. Emerging studies have reported altered levels of MMPs and the Tissue Inhibitors of Metalloproteinases (TIMPs) during MS. A number of pharmaceutical MMP inhibitors are being developed, but they have yet to be recognized for clinical applications. Conclusion: Recently, microRNAs (similar to 21-23-nucleotide, small non-coding, endogenous, single-stranded RNAs) have emerged as a class of promising entities for therapeutic intervention due to their ability to manipulate gene expression. The combined strategy of targeting ECM remodeling through regulation of MMPs by small non-coding RNA has produced encouraging results in pre-clinical studies for cancer and cardiovascular diseases. This review serves to provide insight into the role of microRNAs as modulators of MS and their potential as therapeutics tool through direct and indirect interactions with the MMPs.