Myeloid- and hepatocyte-specific deletion of group VIA calcium-independent phospholipase A2 leads to dichotomous opposing phenotypes during MCD diet-induced NASH

Chutima Jansakun
Heidelberg University Hospital
September 30, 2022
Biochim Biophys Acta Mol Basis Dis
https://pubmed.ncbi.nlm.nih.gov/36334837

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/36334837

Research summary

This study investigates the role of group VIA calcium-independent phospholipase A2 (iPLA2β) in non-alcoholic steatohepatitis (NASH) using myeloid- and hepatocyte-specific Knockout mouse models. The researchers found that deletion of iPLA2β in myeloid cells exacerbated liver inflammation and fibrosis, while its deletion in hepatocytes attenuated these effects during methionine-choline-deficient (MCD) diet-induced NASH. These findings highlight the cell-type-specific functions of iPLA2β in NASH pathogenesis.

Key outcome of the study

iPLA2β plays divergent roles in NASH depending on the cell type: its deletion in myeloid cells worsens liver pathology, while its deletion in hepatocytes has protective effects. This suggests that therapeutic strategies targeting iPLA2β should consider its cell-specific functions.

Model

Myeloid-specific iPLA2β Knockout mice and hepatocyte-specific iPLA2β Knockout mice, generated using Cre-loxP technology with LysM-Cre and Albumin-Cre drivers, respectively.

TARGET:
PNPLA9
Synonyms:
iPLA2β, PLA2G6

Keywords

Non-alcoholic steatohepatitis (NASH), Liver inflammation, Fibrosis, Phospholipase A2, Cell-type-specific gene function

Technical specifications

Conditional Knockout models, Cre-loxP system, LysM-Cre, Albumin-Cre, MCD diet-induced NASH

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