Deceleration of Liver Regeneration by Knockdown of Heme Oxygenase-1 is Associated With Impairment of Liver Injury Recovery After Reduced-Size Liver Transplantation in Rats

Abstract Aim It has been reported that heme oxygenase-1 (HO-1) is upregulated during hepatocyte proliferation. Herein, we used a half-size liver transplantation (HSLT) model to study the impact of HO-1 on liver grafts proliferation. To the best of our knowledge, this is the first time that HO-1 has been characterized as a regulator of liver graft regeneration. Materials and Methods Saline and tin protoporphyrin (SnPP, a HO-1 competitive inhibitor) were separately administered in vehicle and SnPP group before rats HSLT. Plasma samples were collected at 0, 1, 3, and 5 days after HSLT for liver function analysis. Liver tissues were obtained at 0, 1, 3, and 5 days after HSLT for analyses of histologic, apoptosis, and proliferation index by immunohistochemical, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and Western blotting. Results HO-1 level was upregulated by the treatment of HSLT along with accelerated liver proliferation, which was reversed by SnPP. The reduced regeneration by SnPP lead to higher Suzuki’s scores, alanine aminotransferase, and aspartate aminotransferase levels. The interleukin-6 levels, p-Stat3/t-Stat3, c-myc, and c-jun were decreased in the SnPP group than the vehicle group. Conclusions Our findings suggest that inhibition of HO-1 mitigates liver regeneration in part by downregulation of an interleukin-6/Stat3 axis. Targeted specific pharmacologic induction of HO-1 may be applicable in clinical practice.