Gene expression kinetics of muscle-specific micro-RNAs miR-208 and miR-499 in cells treated in vitro with TNF-alpha and INF-gamma

Abstract

Skeletal muscle atrophy is a common phenomenon in many chronic systemic diseases such as sepsis, chronic heart failure, chronic obstructive pulmonary disease, chronic kidney disease, diabetes, AIDS, and cancer. These diseases may be accompanied by a complex metabolic syndrome characterized by muscle wasting, denominated cachexia. The molecular pathways responsible for cachexia are not completely understood, however, evidence suggests that pro-inflammatory cytokines like Tumor Necrosis Factor (TNF)-alpha and Interferon (INF)-gamma have a key role in molecular pathways related to loss of function and muscle mass. The complexity of mechanisms controlling gene expression in this process suggests the involvement of additional regulatory molecules, such as microRNAs; these RNA molecules encoded by the genome regulate the function of skeletal muscle during development and various muscle diseases. MicroRNAs orchestrate common pathways or biological functions, this unique feature gives rise to an effective tool for determining the pathways involved in specific diseases or biological processes. The hypothesis of this work is that muscle atrophy induced by TNF-± and INF-³ changes the kinetics of expression of the MyoMir network components: miR-208b and miR-499 and their target genes Myh7b, Sox6, and Pur-².(AU)