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.

journal_name

Transplant Proc

authors

Cheng B,Xie H,Jia J,Wu M,Guo J,Zhang Y,Liu Y,Zhou J,He N

doi

10.1016/j.transproceed.2019.11.051

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

1001-1006

issue

3

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(19)30907-8

journal_volume

52

pub_type

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