title: MicroRNA-712 restrains macrophage pro-inflammatory responses by targeting LRRK2 leading to restoration of insulin stimulated glucose uptake by myoblasts.
abstract: Chronic inflammatory diseases such as insulin resistance, Type 2 diabetes, neurodegenerative diseases etc., are shown to be caused due to imbalanced activation states of macrophages. MicroRNAs which are transcriptional/post-transcriptional regulators of gene expression drive several pathophysiological processes including macrophage polarization. However the functional role of microRNAs in regulating inflammation induced insulin resistance is ill defined. In our current study we observed that the expression of miR-712 was reduced in macrophages exposed to LPS and IFN-γ. Ectopic expression of miR-712 in RAW 264.7 mouse macrophages impaired the expression of iNOS protein and secretion of pro-inflammatory cytokines such as TNF-α, IL-6 and IFN-β which in turn led to improved insulin stimulated glucose uptake in co-cultured L6 myoblasts. Mechanistically, we identified that miR-712 targets the 3'UTR of a potent inflammatory gene LRRK2 and dampens the phosphorylation of p38 and ERK1/2 kinases. Taken together, our data underscore the regulatory role of miR-712 in restoring insulin stimulated glucose uptake by myoblasts through down-regulating macrophage mediated inflammatory responses.
authors.affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.
authors.forename: Malathi
authors.initials: M
authors.lastname: Talari
authors.affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.
authors.forename: Tapan Kumar Singh
authors.initials: TK
authors.lastname: Nayak
authors.affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.
authors.forename: Vasundhara
authors.initials: V
authors.lastname: Kain
authors.affiliation: Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.
authors.forename: Phanithi Prakash
authors.initials: PP
authors.lastname: Babu
authors.affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.
authors.forename: Parimal
authors.initials: P
authors.lastname: Misra
authors.affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India. Electronic address: kishorep@drils.org.
authors.forename: Kishore V L
authors.initials: KV
authors.lastname: Parsa
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000276:immunology; D005947:Glucose / Q000378:metabolism; D015151:Immunoblotting; D007249:Inflammation / Q000276:immunology; D007333:Insulin Resistance / Q000235:genetics*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000276:immunology*; D008262:Macrophage Activation / Q000235:genetics* / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D035683:MicroRNAs / Q000276:immunology*; D032446:Myoblasts / Q000276:immunology / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C000589251:MIRN712 microRNA, mouse; D035683:MicroRNAs; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; C495279:Lrrk2 protein, mouse; D005947:Glucose
keywords: Inflammation; Macrophage polarization; MicroRNA