Adipocyte Fatty Acid Binding Protein Promotes the Onset and Progression of Liver Fibrosis via Mediating the Crosstalk between Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells

Autor: Ruby L. C. Hoo, Jingjing Li, Erfei Song, Zixuan Zhang, Cunchuan Wang, Jiuyu Zong, Lai Yee Cheong, Aimin Xu, Karen S.L. Lam, Dewei Ye, Xiaoping Wu, Lingling Shu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Liver Cirrhosis
liver sinusoidal endothelial cells
General Chemical Engineering
Science
Regulator
General Physics and Astronomy
Medicine (miscellaneous)
02 engineering and technology
Fatty Acid-Binding Proteins
010402 general chemistry
01 natural sciences
Biochemistry
Genetics and Molecular Biology (miscellaneous)
Transforming Growth Factor beta1
Mice
Transactivation
Paracrine signalling
Animals
Humans
Hedgehog Proteins
General Materials Science
Carbon Tetrachloride
liver fibrosis
Full Paper
Kinase
Chemistry
TGFβ1
JNK Mitogen-Activated Protein Kinases
General Engineering
Endothelial Cells
Full Papers
021001 nanoscience & nanotechnology
Hedgehog signaling pathway
Capillaries
0104 chemical sciences
Cell biology
Disease Models
Animal
Crosstalk (biology)
Gene Expression Regulation
Liver
A‐FABP
Hepatic stellate cell
lipids (amino acids
peptides
and proteins)
hepatic stellate cells
0210 nano-technology
Protein Binding
Signal Transduction
Transforming growth factor
Zdroj: Advanced Science, Vol 8, Iss 11, Pp n/a-n/a (2021)
Advanced Science
ISSN: 2198-3844
Popis: Development of liver fibrosis results in drastic changes in the liver microenvironment, which in turn accelerates disease progression. Although the pathological function of various hepatic cells in fibrogenesis is identified, the crosstalk between them remains obscure. The present study demonstrates that hepatic expression of adipocyte fatty acid binding protein (A‐FABP) is induced especially in the liver sinusoidal endothelial cells (LSECs) in mice after bile duct ligation (BDL). Genetic ablation and pharmacological inhibition of A‐FABP attenuate BDL‐ or carbon tetrachloride‐induced liver fibrosis in mice associating with reduced collagen accumulation, LSEC capillarization, and hepatic stellate cell (HSC) activation. Mechanistically, elevated A‐FABP promotes LSEC capillarization by activating Hedgehog signaling, thus impairs the gatekeeper function of LSEC on HSC activation. LSEC‐derived A‐FABP also acts on HSCs in paracrine manner to potentiate the transactivation of transforming growth factor β1 (TGFβ1) by activating c‐Jun N‐terminal kinase (JNK)/c‐Jun signaling. Elevated TGFβ1 subsequently exaggerates liver fibrosis. These findings uncover a novel pathological mechanism of liver fibrosis in which LSEC‐derived A‐FABP is a key regulator modulating the onset and progression of the disease. Targeting A‐FABP may represent a potential approach against liver fibrosis.
Chronic liver injury upregulates adipocyte fatty acid binding protein (A‐FABP) in liver sinusoidal endothelial cells (LSECs). A‐FABP potentiates LSEC capillarization through activating Hh signaling, thus initiating hepatic stellate cell (HSC) activation. Moreover, LSEC‐derived A‐FABP stimulates TGFβ1 expression in HSCs through activating JNK/c‐Jun signaling. Enhanced TGFβ1 further perpetuates hepatic fibrogenesis.
Databáze: OpenAIRE
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