ASIC1a inhibits cell pyroptosis induced by acid‐induced activation of rat hepatic stellate cells

Autor: Lingjin Kong, Jun Li, Fanrong Wu, Huiping Huang, Rui Jin, Shaohua Luan
Rok vydání: 2020
Předmět:
Liver Cirrhosis
0301 basic medicine
Cations
Divalent
Cell
Nod
General Biochemistry
Genetics and Molecular Biology
Cell Line
Rats
Sprague-Dawley
Extracellular matrix
03 medical and health sciences
0302 clinical medicine
ASIC1a
NLR Family
Pyrin Domain-Containing 3 Protein
medicine
Animals
Humans
Gene silencing
hepatic fibrosis
RNA
Small Interfering
Receptor
lcsh:QH301-705.5
Research Articles
acid‐sensing ion channels
Chemistry
pyroptosis
Caspase 1
Intracellular Signaling Peptides and Proteins
Pyroptosis
Hydrogen-Ion Concentration
Phosphate-Binding Proteins
Recombinant Proteins
Rats
Cell biology
Acid Sensing Ion Channels
CARD Signaling Adaptor Proteins
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Liver
lcsh:Biology (General)
030220 oncology & carcinogenesis
Hepatic stellate cell
Calcium
RNA Interference
hepatic stellate cells
Hepatic fibrosis
Research Article
Zdroj: FEBS Open Bio, Vol 10, Iss 6, Pp 1044-1055 (2020)
FEBS Open Bio
ISSN: 2211-5463
Popis: The activation of hepatic stellate cells (HSCs) is associated with liver fibrosis, the pathological feature of most forms of chronic hepatic damage, and is accompanied by abnormal deposition of the extracellular matrix (ECM). During the pathological process, acid‐sensing ion channel 1a (ASIC1a), which is responsible for Ca2+ transportation, is involved in the activation of HSCs. It has previously been identified that ASIC1a is related to pyroptosis in articular chondrocytes. However, it remains unclear whether ASIC1a restrains pyroptosis during liver fibrosis. Here, we determined that the levels of pyroptosis‐associated speck‐like protein, gasdermin D, caspase‐1, nucleotide‐binding oligomerization domain (NOD)‐like receptor 3, and apoptosis‐associated speck‐like protein (ASC) decreased, while the level of α‐smooth muscle actin and collagen‐I increased upon introduction of ASIC1a into an acid‐induced model. Inhibition or silencing of ASIC1a and the use of Ca2+‐free medium were able to promote the pyroptosis of activated HSCs, which reduced their deposition. In summary, our study indicates that ASIC1a inhibits pyroptosis of HSCs and that inhibition of ASIC1a may be able to promote pyroptosis to relieve liver fibrosis.
Here, we found that acid‐sensing ion channel 1a (ASIC1a) inhibits the pyroptosis of acid‐induced activated hepatic stellate cells, which affects the degree of cell activation. Our results suggest that ASIC1a promotes Ca2+ influx and attenuates the assembly and expression of apoptosis‐associated speck‐like protein, nucleotide‐binding oligomerization domain (NOD)‐like receptor 3, and caspase‐1, thereby reducing the ability of gasdermin D to mediate pyroptosis.
Databáze: OpenAIRE
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