| First Author | Han YH | Year | 2017 |
| Journal | Cell Rep | Volume | 20 |
| Issue | 1 | Pages | 124-135 |
| PubMed ID | 28683306 | Mgi Jnum | J:254850 |
| Mgi Id | MGI:6103930 | Doi | 10.1016/j.celrep.2017.06.017 |
| Citation | Han YH, et al. (2017) RORalpha Induces KLF4-Mediated M2 Polarization in the Liver Macrophages that Protect against Nonalcoholic Steatohepatitis. Cell Rep 20(1):124-135 |
| abstractText | 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 (RORalpha) as a key regulator of M1/M2 polarization in hepatic residential Kupffer cells (KCs) and infiltrated monocyte-derived macrophages. RORalpha 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 RORalpha 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 RORalpha activator, JC1-40, which improved symptoms of NASH. Our results suggest that the M2-promoting effects of RORalpha in liver macrophages may provide better therapeutic strategies against NASH. |
