Mipu1 Inhibits Lipid Accumulation Through Down-Regulation of CD36 in RAW264.7 Cells

Abstract

Background/Aims: Our recent data indicated that Mipu1 overexpression reduces lipid intake and CD36 expression of macrophages in the presence of oxLDL. However, the mechanism of Mipu1 inhibiting lipid accumulation in macrophages is not elucidated. Methods: Real-time quantitative polymerase chain reaction (PCR) and western blot analysis were used to detect expression of Mipu1 and CD36. The promoter activity of CD36 was studied using luciferase assays. Chromatin immunoprecipitation (ChIP) was used to show the recruitment of Mipu1 onto the CD36 promoter. High-performance liquid chromatography and Dil-labeled lipoprotein were used to detect cholesterol accumulation. Results: Here, we show that CD36 overexpression rescues oxLDL-induced cholesterol accumulation in RAW264.7-Mipu1 cells. Analysis of the mouse CD36 promoter revealed two potential Mipu1-response elements (MRE), one of which (from -237bp to -244bp, ACTTAC) was shown, using mutagenesis and deletion analysis, to be functional. Mipu1 was demonstrated to bind to CD36 promoter, and oxLDL treatment resulted in increases in their interaction as assessed by ChIP. Conclusions: It was demonstrated that Mipu1 inhibited the lipid accumulation of macrophages and it down-regulated CD36 expression in the presence of oxLDL.

ZNF667 attenuates leukocyte‐endothelial adhesion via downregulation of P‐selectin in skin flap following remote limb ischemic preconditioning

“…Interestingly, the ZNF667 expression was reduced by siRNA, subsequently influencing the P‐selectin levels in both HDMECs subjected to H/R and HPC. These results resembled those of previous studies (Jiang et al, 2014; S. Qu et al, 2010; S. L. Qu et al, 2015); thus, we hypothesized that ZNF667 may be decreasing the endothelial adhesion by modulating P‐selectin expression (Figure 5b). EMSA has shown that a robust interaction between ZNF667 and P‐selectin probe occurs and that the mutant probe (non‐5′‐CTTA‐3′core sequence) failed to bind to ZNF667.…”

“…The ZNF667 expression in flap tissues also was much higher in the RIPC group. ZNF667 functioned as nuclear transcription repressors, negatively regulated Bax or CD36 (Jiang et al, 2014; S. Qu et al, 2010; S. L. Qu et al, 2015), but the downstream target gene is still not well documented in skin microvessels.…”

“…It contains a KRAB domain at its N‐terminus and 14 successive C 2 H 2 ‐type zinc finger domains at the C‐terminus (Jiang et al, 2007). Previous studies have shown that ZNF667 protein is localized in the nucleus and functions as a transcriptional repressor by binding to its specific DNA‐binding site (5ʹ‐TGTCTTATCGAA‐3ʹ) in the promoter region, and is involved in cell growth, apoptosis, oxidative stress, and lipid accumulation (Jiang et al, 2014; Qu et al, 2010, 2015; G. Wang et al, 2010; K. Wang et al, 2013); however, its role in skin flap with I/R injury has not yet been elucidated.…”

Genome-Wide Re-Sequencing Data Reveals the Population Structure and Selection Signatures of Tunchang Pigs in China

“…ZNF667 (zinc finger protein 667, also referred to as Mipu1) participates in cell growth, apoptosis, oxidative stress, and lipid accumulation. In a study on laryngeal squamous cell carcinoma (LSCC), it was found that ZNF667 is a tumor-suppressing gene [64][65][66][67][68]. ZNF667 can regulate P-selectin expression in specific cells and leukocyte-endothelial adhesion after hypoxia [69].…”

ZNF667 facilitates angiogenesis after myocardial ischemia through transcriptional regulation of VASH1 and Wnt signaling pathway

“…ZNF667 also mediates cytoprotection of HIF1 against hydrogen peroxide-mediated injury in H9c2 cells through transcriptional repression of BAX (25). In addition, ZNF667 can inhibit oxLdL-induced foam cell formation, cell apoptosis and lipid accumulation in macrophages by directly inhibiting the transcription of cd36 (38,39). Nonetheless, to date, no angiogenesis-related gene has been identified as the direct target gene of ZNF667.…”