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ROR alpha Induces KLF4-Mediated M2 Polarization in the Liver Macrophagesthat Protect against Nonalcoholic Steatohepatitis
- Source :
- CELL REPORTS(20): 1, Cell Reports, Vol 20, Iss 1, Pp 124-135 (2017)
- Publication Year :
- 2017
-
Abstract
- The regulation of M1/M2 polarization in liver macrophages is closely associated with the progression of nonalcoholic steatohepatitis (NASH); however, the mechanism involved in this process remains unclear. Here, we describe the orphan nuclear receptor retinoic-acid-related orphan receptor alpha (ROR alpha) as a key regulator of M1/M2 polarization in hepatic residential Kupffer cells (KCs) and infiltrated monocyte-derived macrophages. ROR alpha enhanced M2 polarization in KCs by inducing the kruppel-like factor 4. M2 polarization was defective in KCs and bone-marrow-derived macrophages of the myeloid-specific ROR alpha null mice, and these mice were susceptible to HFD-induced NASH. We found that IL-10 played an important role in connecting the function of M2 KCs to lipid accumulation and apoptosis in hepatocytes. Importantly, M2 polarization was controlled by a ROR alpha activator, JC1-40, which improved symptoms of NASH. Our results suggest that the M2-promoting effects of ROR alpha in liver macrophages may provide better therapeutic strategies against NASH.
- Subjects :
- 0301 basic medicine
Male
Cellular differentiation
Regulator
Kruppel-Like Transcription Factors
Biology
Diet, High-Fat
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Kruppel-Like Factor 4
Mice
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
M2 polarity
Animals
Kupffer cells
RORĪ±
lcsh:QH301-705.5
Cells, Cultured
Orphan receptor
Activator (genetics)
Cell Differentiation
Nuclear Receptor Subfamily 1, Group F, Member 1
KLF4
Cell biology
Interleukin-10
Mice, Inbred C57BL
Interleukin 10
030104 developmental biology
Nuclear receptor
lcsh:Biology (General)
Apoptosis
030220 oncology & carcinogenesis
Immunology
non-alcoholic steatohepatitis
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- CELL REPORTS(20): 1, Cell Reports, Vol 20, Iss 1, Pp 124-135 (2017)
- Accession number :
- edsair.doi.dedup.....c0ac44173e6f35f91dcf8bfc03851108