Journal: Nature Communications
Article Title: A cholesterol-responsive hepatic tRNA-derived small RNA regulates cholesterol homeostasis and atherosclerosis development
doi: 10.1038/s41467-025-67387-z
Figure Lengend Snippet: Seven-week-old male Ldl receptor -deficient ( Ldlr -/- ) mice were treated with tsRNA-Glu-CTC antisense oligonucleotides (ASO) or control ASO twice per week for 7 weeks. The mice were maintained on a normal chow diet (ND) or switched to a high-cholesterol diet (HCD) starting at 8-week-old age. a The schematic of tsRNA-Glu-CTC ASO treatment experiment. Created in BioRender. Zhou, C. ( https://BioRender.com/rj9jwzr ). b – g Body weight ( n = 8,10,10) ( b ), representative photos of collected serum ( c ), serum total cholesterol ( n = 8,10,10) (left panel) and triglyceride ( n = 5,10,10) (right panel) levels ( d ), cholesterol levels of lipoprotein fractions (VLDL-C, LDL-C, and HDL-C) ( n = 8,10,10) ( e ), representative Oil-Red-O (top) and hematoxylin and eosin (bottom) stained liver sections (scale bar =100 μm) ( f ), and hepatic cholesterol ( n = 6,9,6) (left panel) and triglyceride ( n = 6,8,6) (right panel) contents ( g ) of Ldlr -/- mice treated with vehicle control, control ASO, or tsRNA-Glu-CTC ASO (data are shown as mean ± SEM, one-way ANOVA, Bonferroni multiple-comparison test). h Representative images of Oil-red-O-stained sections and quantitative analysis of the atherosclerotic lesion area at the aortic root of Ldlr -/- mice ( n = 7,8,8; mean ± SEM, one-way ANOVA, Bonferroni multiple-comparison test). i Correlation between serum total cholesterol levels and atherosclerotic lesion sizes in Ldlr -/- mice ( n = 16; Correlation was analyzed by Pearson correlation). j Representative images of immunofluorescence staining of CD68 (green) and α-smooth muscle actin (αSMA) (red) at the aortic root of Ldlr -/- mice (scale bar=200 µm). Quantitative analysis of staining area is displayed as indicated ( n = 6,6,6; mean ± SEM, one-way ANOVA, Bonferroni multiple-comparison test). k The expression levels of hepatic lipogenic genes of HCD-fed Ldlr -/- mice treated with tsRNA-Glu-CTC ASO or control ASO were analyzed by quantitative real-time PCR ( n = 6, mean ± SEM, two-tailed Student’s t-test). n represents the number of biological replicates (mice). VLDL-C very low-density lipoprotein cholesterol; LDL-C low density lipoprotein cholesterol; HDL-C high density lipoprotein cholesterol.
Article Snippet: The mice were either fed a normal chow diet (ND) (LabDiet, PicoLab Rodent Diet 5053) for 7 weeks or fed a ND for 1 week and then switched to a HCD for 6 weeks.
Techniques: Control, Staining, Comparison, Immunofluorescence, Expressing, Real-time Polymerase Chain Reaction, Two Tailed Test
