miRNA-133a attenuates lipid accumulation via TR4-CD36 pathway in macrophages.
lipid metabolism is the major causes of atherosclerosis. There is increasing evidence that miR-133a plays an important role in atherosclerosis. However, the regulatory mechanism of miR-133a in macrophages is still unclear. Several lines of evidence indicate that loss of TR4 leads to reduce lipid accumulation in liver and adipose tissues, etc, and lesional macrophages-derived TR4 can greatly increase the foam cell formation through increasing the CD36-mediated the uptake of ox-LDL. Interestingly, computational analysis suggests that TR4 may be a target gene of miR-133a. Here, we examined whether miR-133a regulates TR4 expression in ox-LDL-induced mouse RAW 264.7 macrophages, thereby affecting lipid accumulation. Using ox-LDL-treatment RAW 264.7 macrophages transfected with miR-133a mimics or inhibitors, we have showed that miR-133a can directly regulate the expression of TR4 in RAW 264.7 cells, thereby attenuates CD36-medide lipid accumulation. Furthermore, our studies suggest an additional explanation for the regulatory mechanism of miR-133a regulation to its functional target, TR4 in RAW 264.7 macrophages. Thus, our findings suggest that miR-133a may regulate lipid accumulation in ox-LDL-stimulated RAW 264.7 macrophages via TR4-CD36 pathway.
Department of Cardiovascular Medicine, First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou, Hunan 412000, China.
Xiao-Ping
XP
Peng
Department of Geratology, First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou, Hunan 412000, China. Electronic address: hlhnzyy@163.com.
Lei
L
Huang
Department of Cardiovascular Medicine, First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou, Hunan 412000, China.
Zhi-Hong
ZH
Liu
D000818:Animals; D001483:Base Sequence; D018955:CD36 Antigens / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2 / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2; C099252:oxidized low density lipoprotein
Atherosclerosis; Lipid accumulation; TR4-CD36 pathway; miR-133a