Mesenchymal stem cells increase heme oxygenase 1-activated autophagy in treatment of acute liver failure
| Autor: | Xiaolei Shi, Zhen-ting Tang, Hucheng Ma, Yue Wang, Hao-ran Ding, Jinglin Wang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Biophysics Mesenchymal Stem Cell Transplantation Biochemistry Rats Sprague-Dawley Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Autophagy medicine Animals LY294002 Molecular Biology PI3K/AKT/mTOR pathway Inflammation business.industry digestive oral and skin physiology Mesenchymal stem cell Autophagosomes Mesenchymal Stem Cells Cell Biology Liver Failure Acute Up-Regulation Heme oxygenase Transplantation 030104 developmental biology medicine.anatomical_structure Liver chemistry 030220 oncology & carcinogenesis Hepatocyte Hepatocytes Cancer research Liver function business Proto-Oncogene Proteins c-akt Heme Oxygenase-1 Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 508:682-689 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2018.11.146 |
| Popis: | In recent years, transplantation of mesenchymal stem cells (MSCs) has attracted much attention as a potential cell-based therapy for acute liver failure (ALF). As an inducible enzyme, heme oxygenase 1 (HO-1) has been reported to have cytoprotective, anti-apoptotic and immunoregulatory effects. Autophagy, a conserved catabolic process in cells, may be an important pathway for MSCs to treat ALF. In this study, we aimed to explore whether MSCs treat ALF by regulating autophagy and whether HO-1 was involved in the same pathway. Bone marrow-derived MSCs were isolated from Sprague-Dawley rats and cultured according to an established protocol. Co-culture systems of MSCs and hepatocytes were used to assess autophagy in the treatment of ALF. Meanwhile, MSCs were transplanted into rats with d-galactosamine (Gal)-induced ALF. Autophagy inhibitor (3-methyladenine, 3-MA), HO-1 inhibitor (zinc protoporphyrin, ZnPP) and PI3K specific inhibitor (LY294002) were employed in the study. Blood samples and liver tissues were collected before euthanasia. Survival rate, liver function, inflammatory factors, histology, Ki67 and TUNEL staining were determined. MSCs transplantation alleviated ALF both in vivo and in vitro. Autophagy and autophagy-related proteins were significantly up-regulated during MSCs treatment. 3-MA attenuated the therapeutic effect of MSCs. Administration of LY294002 before ALF induction inhibited hepatocyte autophagy. During the MSCs treatment, the HO-1 expression was increased, while inhibiting HO-1 attenuated the therapeutic effect of MSCs as well as hepatocyte autophagy. These findings suggested MSCs could alleviate ALF by increasing the HO-1 expression, which played an important role in activating autophagy through PI3K/AKT signaling pathway. |
| Databáze: | OpenAIRE |
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