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MicroRNA 33 Regulates the Population of Peripheral Inflammatory Ly6Chigh Monocytes through Dual Pathways
- Source :
- Molecular and Cellular Biology
- Publication Year :
- 2018
- Publisher :
- Informa UK Limited, 2018.
-
Abstract
- MicroRNA 33 (miR-33) targets ATP-binding cassette transporter A1 (ABCA1), and its deficiency increases serum high-density lipoprotein (HDL)-cholesterol (HDL-C) and ameliorates atherosclerosis. Although we previously reported that miR-33 deficiency increased peripheral Ly6Chigh monocytes on an ApoE-deficient background, the effect of miR-33 on the monocyte population has not been fully elucidated, especially in a wild-type (WT) background. We found that Ly6Chigh monocytes in miR-33−/− mice were decreased in peripheral blood and increased in bone marrow (BM). Expansion of myeloid progenitors and decreased apoptosis in Lin− Sca1+ c-Kit+ (LSK) cells were observed in miR-33−/− mice. A BM transplantation study and competitive repopulation assay revealed that hematopoietic miR-33 deficiency caused myeloid expansion and increased peripheral Ly6Chigh monocytes and that nonhematopoietic miR-33 deficiency caused reduced peripheral Ly6Chigh monocytes. Expression of high-mobility group AT-hook 2 (HMGA2) targeted by miR-33 increased in miR-33-deficient LSK cells, and its knockdown abolished the reduction of apoptosis. Transduction of human apolipoprotein A1 and ABCA1 in WT mouse liver increased HDL-C and reduced peripheral Ly6Chigh monocytes. These data indicate that miR-33 deficiency affects distribution of inflammatory monocytes through dual pathways. One pathway involves the enhancement of Hmga2 expression in hematopoietic stem cells to increase Ly6Chigh monocytes, and the other involves the elevation of HDL-C to decrease peripheral Ly6Chigh monocytes.
- Subjects :
- Male
0301 basic medicine
Myeloid
Mice, Knockout, ApoE
Population
Apoptosis
Biology
Monocytes
Mice
03 medical and health sciences
Apolipoproteins E
stem cells
Transduction, Genetic
medicine
Animals
Antigens, Ly
Humans
HDL-C
Progenitor cell
education
Molecular Biology
Myeloid Progenitor Cells
Mice, Knockout
education.field_of_study
microRNA
Apolipoprotein A-I
Monocyte
Cholesterol, HDL
Cell Biology
Atherosclerosis
Hematopoietic Stem Cells
Recombinant Proteins
Mice, Inbred C57BL
Transplantation
MicroRNAs
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
Cancer research
Bone marrow
Stem cell
Research Article
ATP Binding Cassette Transporter 1
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....b7146e0e57377069c72ed55cc2e28be2