miR-145 improves metabolic inflammatory disease through multiple pathways.

Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes, yet the mechanisms are not completely understood. Here, we demonstrated that serum LPS levels were significantly higher in newly diagnosed diabetic patients than in normal control. miR-145 level in peripheral blood mononuclear cells decreased in type 2 diabetics. LPS repressed the transcription of miR-143/145 cluster and decreased miR-145 levels. Attenuation of miR-145 activity by anti-miR-145 triggered liver inflammation and increased serum chemokines in C57BL/6 J mice. Conversely, lentivirus-mediated miR-145 overexpression inhibited macrophage infiltration, reduced body weight, and improved glucose metabolism in db/db mice. And miR-145 overexpression markedly reduced plaque size in the aorta in ApoE-/- mice. Both OPG and KLF5 were targets of miR-145. miR-145 repressed cell proliferation and induced apoptosis partially by targeting OPG and KLF5. miR-145 also suppressed NF-κB activation by targeting OPG and KLF5. Our findings provide an association of the environment with the progress of metabolic disorders. Increasing miR-145 may be a new potential therapeutic strategy in preventing and treating metabolic diseases such as type 2 diabetes and atherosclerosis.

Identification of the novel protein FAM172A, and its up-regulation by high glucose in human aortic smooth muscle cells.

The family with sequence similarity 172, member A (FAM172A) is a hypothetical protein. We recently cloned the FAM172A gene from normal human aortic tissues. In a previous study we also showed that the FAM172A gene was up-regulated by high glucose levels in macrophages. In the present study, we further identified the FAM172A protein at the level of translation and studied the effects of high glucose levels on its expression in human aortic smooth muscle cells. The FAM172A gene was subcloned into the eukaryotic expression vectors, PDC315 and pEGFP-N2. The cloned sequence shows an open reading frame of 1251 nucleotides encoding a protein of 416 amino acids. We further expressed the recombinant FAM172A protein and generated rabbit anti-human FAM172A polyclonal antibodies. The FAM172A protein was identified for the first time at the translation level by Western blot analysis. Western blotting also demonstrated that the FAM172A protein could be detected in human aortic endothelial, human aortic smooth muscle cells and THP-1-derived macrophages, the highest expression being observed in the human aortic smooth muscle cells. By a combination of bioinformatics and confocal laser scanning microscopy, we found that the FAM172A protein in HEK293 cells, was mainly located in the nucleus, and that there was an Arb2 conserved domain in the FAM172A protein sequence. We also presented evidence that the FAM172 protein expression in human aortic smooth muscle cells was up-regulated by high glucose levels in a concentration-dependent and time-course manner. We speculated that as a novel protein, FAM172A could be involved in the pathogenesis of high glucose-induced vascular damage.