The role of pannexin1 channels in non-alcoholic steatohepatitis: therapeutic and diagnostic relevance.

Pannexin1 (Panx1) channels mediate paracrine signaling and have
emerged as key players in inflammation, which is associated with a
plethora of diseases. Among those is non-alcoholic steatohepatitis
(NASH), being the predominant type of chronic liver disease in
Western countries. The present project will investigate the role of
Panx1 channels in NASH at the transcriptional, translational and
functional level using spheroid co-cultures of primary human
hepatocytes and non-parenchymal human liver cells. This will be
complemented by studying Panx1 expression in liver samples of
NASH patients. Subsequently, Panx1 expression and/or channel
functionality will be experimentally suppressed in the NASH spheroid
co-culture system as well as in a human-relevant mouse model of
NASH, and effects will be studied on the transcriptome, lipid
accumulation, inflammation and cell death. Through the combination
of fundamental, translational and clinical research and by relying on
in vitro, ex vivo and in vivo experimentation, this project is considered
of high pharmaceutical and clinical relevance, as it may introduce
novel strategies for the treatment and diagnosis of NASH.