Protective effects of heme oxygenase-1-transduced bone marrow-derived mesenchymal stem cells on reduced‑size liver transplantation: Role of autophagy regulated by the ERK/mTOR signaling pathway

Wang,Raorao; Shen,Zhongyang; Yang,Liu; Yin,Mingli; Zheng,Weiping; Wu,Bin; Liu,Tao; Song,Hongli

doi:10.3892/ijmm.2017.3121

Protective effects of heme oxygenase-1-transduced bone marrow-derived mesenchymal stem cells on reduced‑size liver transplantation: Role of autophagy regulated by the ERK/mTOR signaling pathway

Authors:
- Raorao Wang
- Zhongyang Shen
- Liu Yang
- Mingli Yin
- Weiping Zheng
- Bin Wu
- Tao Liu
- Hongli Song
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Affiliations: Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, P.R. China
Published online on: September 6, 2017 https://doi.org/10.3892/ijmm.2017.3121
Pages: 1537-1548
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Autophagy is a critical lysosomal pathway that degrades cytoplasmic components to maintain cell homeostasis and provide substrates for energy metabolism. A study revealed that heme oxygenase-1 (HO-1)-transduced bone marrow-derived mesenchymal stem cells (BM-MSCs) could protect 50% reduced-size liver transplantation (RSLT) in a rat model. However, the mechanisms remain mostly unknown. The aim of the present study was to explore the effects and related mechanism of autophagy on the protection conferred by HO-1-transduced BM-MSCs (HO-1/BM-MSCs) on 50% RSLT in a rat model. The authors established an acute rejection model following 50% RSLT in rats, with recipients divided into three groups receiving treatment with BM-MSCs, HO-1/BM-MSCs or normal saline (NS) injected through the dorsal penile vein. Transplanted liver tissues at 0, 1, 3, 5, 7, 10 and 14 days following transplantation were acquired for further analysis. The results indicated that the expression of autophagy-related proteins LC3 and Beclin-1 increased, the levels of ERK and p-ERK increased, and the levels of mammalian target of rapamycin (mTOR) and p-mTOR decreased in the HO-1/BM-MSCs. These observations indicated that autophagy is involved in the protective effects of HO-1/BM-MSCs on liver grafts following RSLT, possibly via upregulation of autophagy-related proteins through the ERK/mTOR signaling pathway.

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