RETRACTED ARTICLE: The myocardial infarction-associated transcript 2 inhibits lipid accumulation and promotes cholesterol efflux in oxidized low-density lipoprotein-induced THP-1-derived macrophages via inhibiting mitogen-activated protein kinase signaling and activating the nuclear factor erythroid-related factor 2 signaling pathway

Abstract

Dysregulated lipid metabolism of macrophages contributes to thrombosis and antiphospholipid syndrome (APS). The long non-coding RNAs (lncRNA) myocardial infarction-associated transcript 2 (Mirt2) has been reported to inhibit inflammation and lipid accumulation; therefore, this study intended to clarify whether Mirt2 served a role in lipid metabolism. THP-1-derived macrophages with or without Mirt2-knockdown or overexpression, were exposed to oxidized low-density lipoprotein (ox-LDL), then cell migration, lipid accumulation, cholesterol efflux and inflammation were assessed using wound healing, oil red staining, commercial kits and western blot assays. Besides, ML385 was used to treat THP-1-derived macrophages to inhibit nuclear factor erythroid-related factor 2 (NRF2) expression. The expression of proteins involved in the above processes were measured by western blot. Results demonstrated that phorbol 12-myristate 13-acetate (PMA) significantly increased Mirt2 expression in THP-1 cells. Mirt2-knockdown enhanced ox-LDL-induced macrophage migration, lipid accumulation, inflammation, and inhibited cholesterol efflux. By contrast, Mirt2 overexpression displayed the opposite effects. Furthermore, Mirt2-knockdown inhibited NRF2 signaling and enhanced mitogen-activated protein kinase (MAPK) signaling, while Mirt2 overexpression displayed the opposite effects. Finally, the NRF2 inhibitor ML385 significantly reversed the above effects of Mirt2. In summary, Mirt2 served an important role in regulating lipid metabolism in macrophages via inhibiting MAPK signaling and activating the NRF2 signaling pathway.

ARID5B‐mediated LINC01128 epigenetically activated pyroptosis and apoptosis by promoting the formation of the BTF3/STAT3 complex in β2GPI/anti‐β2GPI‐treated monocytes

“…ARID5B‐bound regions are predominantly associated with active transcription, 39 and lncRNA dysfunction has been shown to lead to autoimmune disorders and may contribute to APS 6 . Therefore, anti‐ARID5B CUT&Tag was performed using THP‐1 cells to screen downstream lncRNAs involved in APS pathogenesis (Supporting Information S4).…”

“…ARID5B‐bound regions are predominantly associated with active transcription, 39 and lncRNA dysfunction has been shown to lead to autoimmune disorders and may contribute to APS. 6 Therefore, anti‐ARID5B CUT&Tag was performed using THP‐1 cells to screen downstream lncRNAs involved in APS pathogenesis (Supporting Information S4 ). The results validated eight lncRNAs located within upstream 5 kb of the ARID5B's TSS (Figure 2A ), and their transcription might be regulated by ARID5B.…”

“…In addition, they are involved in activating endothelial cells, neutrophils, platelets and monocytes and releasing inflammatory mediators and coagulation factors. 2 , 3 Although in vitro studies and animal experiments have revealed the involvement of epigenetics in the pathogenesis of APS, including long non‐coding RNAs (lncRNAs) and cytosine‐phosphate‐guanine (CpG) methylation at the promoters of genes, 4 , 5 , 6 the mechanisms of histone modification in its occurrence and development remain to be elucidated. 3 , 7 …”

“…In addition, they are involved in activating endothelial cells, neutrophils, platelets and monocytes and releasing inflammatory mediators and coagulation factors. 2,3 Although in vitro studies and animal experiments have revealed the involvement of epigenetics in the pathogenesis of APS, including long noncoding RNAs (lncRNAs) and cytosine-phosphate-guanine (CpG) methylation at the promoters of genes, [4][5][6] the mechanisms of histone modification in its occurrence and development remain to be elucidated. 3,7 Trimethylation of histone 3 lysine 4 (H3K4me3) is a major histone modification, resulting in dynamic alterations of chromatin accessibility and the expression of inflammation-related genes, suggesting its potential role in the pathogenesis of APS.…”

Proteomics analysis of plasm exosomes in early pregnancy among normal pregnant women and those with antiphospholipid syndrome

“…Numerous studies have confirmed the crucial roles of lipid metabolism in early embryo development, implantation, and uterine receptivity [ 26 ]. Meanwhile, dysregulated lipid metabolism is associated with the development and poorer prognosis of APS and thrombosis [ 27 , 28 ]. Our proteomics research has revealed a tight association between plasm exosomes from APS pregnant individuals and lipid metabolism.…”