Insulin-like growth factor binding protein-3 (IGFBP-3) is known to interfere NF-ΚB signaling pathway in response to a diverse range of stimuli. Liver ischemia/reperfusion injury is associated with rapid activation of NF-ΚB signaling, but the role of NF-ΚB in hepatic ischemia/reperfusion injury remains controversial. The NF-ΚB signaling pathway mediates both protective and deleterious effects in the liver. Here, we examined whether IGFBP-3 inhibited or aggravated hepatic ischemia/reperfusion injury. We overexpressed IGFBP-3 in the liver of C57BL/6 mice. Mice underwent 45 min of partial hepatic ischemia and were then reperfused. Mice subjected to ischemia/reperfusion injury showed increased NF-ΚB activation, as evidenced by phosphorylation of IΚBΑ and nuclear translocation of NF-ΚB. Prior infection with Ad-IGFBP-3 attenuated NF-ΚB activation. Serum aminotransferases, hepatocellular necrosis, and hepatic neutrophil infiltration were markedly increased compared to those of uninfected or control virus infected mice. In addition, IGFBP-3 mutant devoid of IGF binding affinity but retains IGFBP-3 receptor binding ability (Ad-IGFBP-3GGG) also exhibited similar effects as Ad-IGFBP3 did, suggesting a ligand-independent effect of IGFBP-3 on liver damage. These results suggest that inhibition of NF-ΚB activation by IGFBP-3 aggravated partial hepatic ischemia/reperfusion injury. Understanding how the NF-ΚB pathway plays a role in directing a clinical outcome may lead to better prospects of more rational approaches to reduce post-ischemic liver injury.
To cite this abstract in AMA style:Yang J, Yu H, Park B, Hwang H, Cho B. Aggravation of Post-Ischemic Liver Injury by Overexpression of IGFBP-3 [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/aggravation-of-post-ischemic-liver-injury-by-overexpression-of-igfbp-3/. Accessed October 27, 2020.
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