Guest editorial

Highlight report: Role of the ATP-releasing Panx channels in liver fibrosis

Daniela Fernanda González Leiva1[*]

1IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund, GERMANY

EXCLI J 2019;18:Doc8


Recently Sara Crespo Yanguas and colleagues from the University of Brussel published a study about the role of pannexin1 in the pathogenesis of liver fibrosis (Crespo Yanguas et al., 2018[3]). Panx channels are known as mediators of ATP release (Dahl, 2015[4]). After injury cells may release ATP and uridine-5'-triphosphate into the extracellular space. The released ATP attracts immune cells to the area of damage (Davalos et al., 2005[5]; Chekeni et al., 2010[2]). In cardiac fibrosis cardiomyocytes have been shown to release ATP via pannexin1 which contributes to activation of fibroblasts (Dolmatova et al., 2012[6]). However, in liver the role of pannexin1 in liver fibrosis remains unknown. Therefore, the authors compared pannexin1 knockout and wild-type mice after CCl4 treatment for 8 weeks and after bile duct ligation (Crespo Yanguas et al., 2018[3]).

Interestingly, pannexin1 knockout mice showed reduced collagen content, stellate cell activation, and inflammation compared to wild-type mice. Therefore, the release of ATP seems to contribute to myofibroblast activation also in the liver. In contrast to the CCl4- fibrosis model, bile duct ligation led to more hepatocellular injury and a stronger immune response in the pannexin1 knockout than in wild-type mice.

It is not surprising that different consequences are observed in the CCl4 and the bile duct ligation models. CCl4 is a model of pericentral liver damage where a fraction of approximately 40 % of hepatocytes in the centre of the lobule are killed (Hoehme et al., 2010[16]; Hammad et al., 2017[14]; Bartl et al., 2015[1]). It seems plausible that the ATP released from these damaged hepatocytes activates stellate cells (Leist et al., 2017[18]). In contrast, bile duct ligation leads to a ductular response with proliferation of cholangiocytes, branching and looping of bile ducts, leading to a denser mesh of interlobular bile ducts around portal veins (Vartak et al., 2016[21]; Jansen et al., 2017[17]). Simultaneously, periportal fibrosis occurs (Ghallab et al., 2018[10]). It is interesting that this phenomenon is enhanced by the pannexin1 knockout, although the responsible mechanism still has to be elucidated.

Currently, hepatotoxicity in vivo (Stöber, 2016[20]; Du et al., 2017[7]; Reif et al., 2017[19]; Hammad et al., 2018[15]; Ghallab et al., 2016[9]) as well as mechanistic studies in hepatocyte in vitro systems represent very active research areas (Ghallab, 2017[8]; Godoy et al., 2013[11], 2015[12], 2016[13]). In this rapidly progressing field Sara Crespo Yanguas and colleagues made an important contribution by revealing the role of ATP-release channels in the pathogenesis of liver fibrosis.



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[*] Corresponding Author:

Daniela Fernanda González Leiva, IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund, GERMANY, eMail: