Connexin32 deficiency exacerbates carbon tetrachloride-induced hepatocellular injury and liver fibrosis in mice.

Objective: Liver fibrosis results from the perpetuation of the normal wound healing response to several
types of injury. Despite the wealth of knowledge regarding the involvement of intracellular and extracellular
signaling pathways in liver fibrogenesis, information about the role of intercellular communication
mediated by gap junctions is scarce.
Methods: In this study, liver fibrosis was chemically induced by carbon tetrachloride in mice lacking
connexin32, the major liver gap junction constituent. The manifestation of liver fibrosis was evaluated
based on a series of read-outs, including collagen morphometric and mRNA analysis, oxidative stress,
apoptotic, proliferative and inflammatory markers.
Results: More pronounced liver damage and enhanced collagen deposition were observed in connexin32
knockout mice compared to wild-type animals in experimentally triggered induced liver fibrosis.
No differences between both groups were noticed in apoptotic signaling nor in inflammation markers.
However, connexin32 deficient mice displayed decreased catalase activity and increased malondialdehyde
levels.
Conclusion: These findings could suggest that connexin32-based signaling mediates tissue resistance
against liver damage by the modulation of the antioxidant capacity. In turn, this could point to a role
for connexin32 signaling as a therapeutic target in the treatment of liver fibrosis.