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LECT2 as a hepatokine links liver steatosis to inflammation via activating tissue macrophages in NASH
- Source :
- Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021), Scientific Reports
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
Abstract
- It remains unclear how hepatic steatosis links to inflammation. Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine that senses fat in the liver and is upregulated prior to weight gain. The aim of this study was to investigate the significance of LECT2 in the development of nonalcoholic steatohepatitis (NASH). In human liver biopsy samples, elevated LECT2 mRNA levels were positively correlated with body mass index (BMI) and increased in patients who have steatosis and inflammation in the liver. LECT2 mRNA levels were also positively correlated with the mRNA levels of the inflammatory genes CCR2 and TLR4. In C57BL/6J mice fed with a high-fat diet, mRNA levels of the inflammatory cytokines Tnfa and Nos2 were significantly lower in Lect2 KO mice. In flow cytometry analyses, the number of M1-like macrophages and M1/M2 ratio were significantly lower in Lect2 KO mice than in WT mice. In KUP5, mouse kupffer cell line, LECT2 selectively enhanced the LPS-induced phosphorylation of JNK, but not that of ERK and p38. Consistently, LECT2 enhanced the LPS-induced phosphorylation of MKK4 and TAB2, upstream activators of JNK. Hepatic expression of LECT2 is upregulated in association with the inflammatory signature in human liver tissues. The elevation of LECT2 shifts liver residual macrophage to the M1-like phenotype, and contributes to the development of liver inflammation. These findings shed light on the hepatokine LECT2 as a potential therapeutic target that can dissociate liver steatosis from inflammation.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
CCR2
Liver cytology
Kupffer Cells
Science
Gene Expression
Inflammation
Diet, High-Fat
Article
Proinflammatory cytokine
Cell Line
03 medical and health sciences
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Internal medicine
medicine
Animals
Molecular Targeted Therapy
RNA, Messenger
Obesity
Phosphorylation
Non-alcoholic steatohepatitis
Adaptor Proteins, Signal Transducing
Multidisciplinary
business.industry
Kupffer cell
JNK Mitogen-Activated Protein Kinases
Macrophage Activation
medicine.disease
Up-Regulation
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Liver
030220 oncology & carcinogenesis
TLR4
Intercellular Signaling Peptides and Proteins
Medicine
Tumor necrosis factor alpha
Steatosis
medicine.symptom
business
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....5ac37d52a4c5c8daf15c59aa312efee8