Ecto-nucleotidase triphosphate diphosphohydrolase-2 (NTPDase2) is an ecto-enzyme that
is expressed on portal fibroblasts in the liver that modulates P2 receptor signaling by regulating
local concentrations of extracellular ATP and ADP. NTPDase2 has protective properties in liver
fibrosis and may impact bile duct epithelial turnover. Here, we study the role of NTPDase2 in acute
liver injury using an experimental model of acetaminophen (APAP) intoxication in mice with global
deletion of NTPDase2. Acute liver toxicity was caused by administration of acetaminophen in wild
type (WT) and NTPDase2-deficient (Entpd2 null) mice. The extent of liver injury was compared
by histology and serum alanine transaminase (ALT). Markers of inflammation, regeneration and
fibrosis were determined by qPCR). We found that Entpd2 expression is significantly upregulated
after acetaminophen-induced hepatotoxicity. Entpd2 null mice showed significantly more necrosis
and higher serum ALT compared to WT. Hepatic expression of IL-6 and PDGF-B are higher in Entpd2
null mice. Our data suggest inducible and protective roles of portal fibroblast-expressed NTPDase2
in acute necrotizing liver injury. Further studies should investigate the relevance of these purinergic
pathways in hepatic periportal and sinusoidal biology as such advances in understanding might
provide possible therapeutic targets.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89304 |
| Date | 26 January 2024 |
| Creators | Feldbrügge, Linda, Splith, Katrin, Kämmerer, Ines, Richter, Sandra, Riddermann, Anna, Ortiz Galindo, Santiago Andres, Krenzien, Felix, Müller, Tobias, Csizmadia, Eva, Pratschke, Johann, Robson, Simon C., Schmelzle, Moritz |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 5998 |
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