Inhibition of aquaporin-3 in macrophages by a monoclonal antibody as potential therapy for liver injury.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33168815.
- Also identified by DOI 10.1038/s41467-020-19491-5 and PMC identifier 7653938.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Aquaporin 3 (AQP3) is a transporter of water, glycerol and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) that is expressed in various epithelial cells and in macrophages. Here, we developed an anti-AQP3 monoclonal antibody (mAb) that inhibited AQP3-facilitated H<sub>2</sub>O<sub>2</sub> and glycerol transport, and prevented liver injury in experimental animal models. Using AQP3 knockout mice in a model of liver injury and fibrosis produced by CCl<sub>4</sub>, we obtained evidence for involvement of AQP3 expression in nuclear factor-κB (NF-κB) cell signaling, hepatic oxidative stress and inflammation in macrophages during liver injury. The activated macrophages caused stellate cell activation, leading to liver injury, by a mechanism involving AQP3-mediated H<sub>2</sub>O<sub>2</sub> transport. Administration of an anti-AQP3 mAb, which targeted an extracellular epitope on AQP3, prevented liver injury by inhibition of AQP3-mediated H<sub>2</sub>O<sub>2</sub> transport and macrophage activation. These findings implicate the involvement of macrophage AQP3 in liver injury, and provide evidence for mAb inhibition of AQP3-mediated H<sub>2</sub>O<sub>2</sub> transport as therapy for macrophage-dependent liver injury.
Medical subject headings
- Antibodies, Monoclonal
- Aquaporin 3
- Chemical and Drug Induced Liver Injury
- Macrophages