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RORα Induces KLF4-Mediated M2 Polarization in the Liver Macrophages that Protect against Nonalcoholic Steatohepatitis

Han, Yong-Hyun ; Kim, Hyeon-Ji ; Na, Hyelin ; Nam, Min-Woo ; Kim, Ju-Yeon ; Kim, Jun-Seok ; Koo, Seung-Hoi ; Lee, Mi-Ock

Cell reports (Cambridge), 2017-07, Vol.20 (1), p.124-135 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
RORα Induces KLF4-Mediated M2 Polarization in the Liver Macrophages that Protect against Nonalcoholic Steatohepatitis
Autor: Han, Yong-Hyun ; Kim, Hyeon-Ji ; Na, Hyelin ; Nam, Min-Woo ; Kim, Ju-Yeon ; Kim, Jun-Seok ; Koo, Seung-Hoi ; Lee, Mi-Ock
Assuntos: Animals ; Cell Differentiation ; Cells, Cultured ; Diet, High-Fat - adverse effects ; Interleukin-10 - metabolism ; KLF4 ; Kruppel-Like Transcription Factors - metabolism ; Kupffer cells ; Kupffer Cells - cytology ; Kupffer Cells - metabolism ; M2 polarity ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease - etiology ; Non-alcoholic Fatty Liver Disease - metabolism ; non-alcoholic steatohepatitis ; Nuclear Receptor Subfamily 1, Group F, Member 1 - genetics ; Nuclear Receptor Subfamily 1, Group F, Member 1 - metabolism ; RORα
É parte de: Cell reports (Cambridge), 2017-07, Vol.20 (1), p.124-135
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 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 α (RORα) as a key regulator of M1/M2 polarization in hepatic residential Kupffer cells (KCs) and infiltrated monocyte-derived macrophages. RORα 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 RORα 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 RORα activator, JC1-40, which improved symptoms of NASH. Our results suggest that the M2-promoting effects of RORα in liver macrophages may provide better therapeutic strategies against NASH. [Display omitted] •RORα enhances M2 polarization in liver macrophages, including Kupffer cells and BMDMs•Myeloid-specific knockout of RORα enhances susceptibility to HFD-induced NASH•M2 Kupffer cells protect hepatocytes injury by secreting IL-10•RORα activator induces M2 polarity switch in Kupffer cells and protects against NASH Han et al. find that RORα is a key regulator of M1/M2 polarization in liver macrophages. Myeloid-specific knockout of RORα display decreased M2/M1 ratio in Kupffer cells and enhanced susceptibility to nonalcoholic steatohepatitis. This function of RORα may suggest therapeutic strategies for nonalcoholic steatohepatitis.
Editor: United States: Elsevier Inc
Idioma: Inglês

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RORα Induces KLF4-Mediated M2 Polarization in the Liver Macrophages that Protect against Nonalcoholic Steatohepatitis

Han, Yong-Hyun ; Kim, Hyeon-Ji ; Na, Hyelin ; Nam, Min-Woo ; Kim, Ju-Yeon ; Kim, Jun-Seok ; Koo, Seung-Hoi ; Lee, Mi-Ock

United States: Elsevier Inc

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