The liver injury following ischemia and reperfusion is worse in experimental knockout heterozygote mouse model for expression of connexin 43

Abstract

Purpose:To evaluate that Connexin (Cx43) plays a role in lesions after hepatic ischemia/reperfusion (IR) injury.Methods:We use Cx43 deficient model (heterozygotes mice) and compared to a wild group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes (AST, ALT, GGT) and histology.Results:The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group.Conclusions:This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.

Intercellular Transmission of Hepatic ER Stress in Obesity Disrupts Systemic Metabolism

“…In addition, inhibiting Cx43 following bile duct ligation produces detrimental effects with markedly greater hepatocellular necrosis (Balasubramaniyan et al, 2013). Liver injury following ischemia and reperfusion was worse in Cx43 heterozygous mice, resulting in increased liver necrosis (Trevisan et al, 2019), and Cx43 haploinsufficiency resulted in excessive liver fibrosis by CCl4 -induced hepatic injury (Cogliati et al, 2011), highlighting the adaptive role of Cx43 and cell-cell communication in the response of the liver to acute insults. Similarly, when WT and Cx43L-KO mice were exposed to tunicamycin, we observed a key adaptive role for Cx43-mediated hepatocyte coupling in the tissue response to this acute injury.…”