Long non-coding RNA myocardial infarction-associated transcript promotes 1-Methyl-4-phenylpyridinium ion-induced neuronal inflammation and oxidative stress in Parkinson's disease through regulating microRNA-221-3p/ transforming growth factor /nuclear factor E2-related factor 2 axis.

This study attempted to evaluate the role of long non-coding RNA myocardial infarction-associated transcript (LncRNA MIAT) in Parkinson's disease (PD). The mouse model was established through intraperitoneal injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and in vitro model was induced by administrating cell with 1-Methyl-4-phenylpyridinium ion (MPP+). Rotarod test was conducted to evaluate the motor coordination of PD mice. In order to investigate the roles of LncRNA MIAT in neuronal inflammation and oxidative stress, MIAT shRNA (shMIAT) was transfected into MPP+-treated cells, and cell viability, cell apoptosis and oxidative stress response were evaluated. To evaluate the interactions between LncRNA MIAT and microRNA-221-3p (miR-221-3p)/TGF-ß1/Nrf2, miR-221-3p mimic, miR-221-3p inhibitor, NC-inhibitor and transforming growth factor-ß1 shRNA (shTGF-ß1) were subsequently transfected into MPP+-treated cells. Dual-luciferase reporter gene assays were performed to determine the interaction of miR-221-3p with MIAT or TGFB receptor 1 (TGFBR1). The expressions of LncRNA MIAT, miR-221-3p, TGFBR1, transforming growth factor (TGF-ß1) and nuclear factor E2-related factor 2 (Nrf2) were measured by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and immunoblotting. As a result, LncRNA MIAT was abundantly expressed in PD mice and cells, while downregulation of LncRNA MIAT promoted the survival of neurons, inhibited apoptosis and oxidative stress in neurons. LncRNA MIAT bound to miR-221-3p, and there was a negative correlation between miR-221-3p and LncRNA MIAT expression. In addition, miR-221-3p targeted TGFBR1 and suppressed TGF-ß1 expression but increased Nrf2 expression. LncRNA MIAT promoted MPP+-induced neuronal injury in PD via regulating TGF-ß1/Nrf2 axis through binding with miR-221-3p.

B and T cell responses to the spliceosomal heterogeneous nuclear ribonucleoproteins A2 and B1 in normal and lupus mice.

Autoantibodies directed against spliceosomal heterogeneous nuclear ribonucleoproteins (hnRNPs) are a typical feature of rheumatoid arthritis, systemic lupus erythematosus, and mixed-connective tissue disease. With the aim of investigating a potential pathogenic role of these Abs, we have studied the Ab response to A2/B1 hnRNPs in different murine models of lupus. The specificity of anti-A2/B1 Abs was tested with a series of 14 overlapping synthetic peptides covering the region 1-206 of A2 that contains most of the epitopes recognized by patients' Abs. A major epitope recognized very early during the course of the disease by Abs from most of MRL lpr/lpr mice but not from other lupus mice and from mice of different MHC haplotypes immunized against B1 was identified in residues 50-70. This peptide contains a highly conserved sequence RGFGFVTF also present in other hnRNPs and small nuclear ribonucleoproteins. Abs reacting with a second A2 epitope identified in residues 35-55 were detectable several weeks later, suggesting an intramolecular B cell epitope spreading during the course of the disease. We identified several T cell epitopes within the region 35-175 that generated an effective Th cell response with IL-2 and IFN-gamma secretion in nonautoimmune CBA/J mice sharing the same MHC haplotype H-2k as MRL/lpr mice. None of the peptides stimulated T cells primed in vivo with B1. Because Abs to peptide 50-70 were detected significantly earlier than Abs reacting with other A2 peptides and the protein itself, it is possible that within the protein, this segment contains residues playing an initiator role in the induction of the anti-A2/B1 and antispliceosome Ab response.