MG-132 enhances MSCs survival and IL-10 secretion under hypoxia and serum deprivation condition.
- Author:
Zong-Wei LI
1
;
Rong FU
;
Ya-Rui ZHAO
;
Chao ZHAO
;
Zhuo-Yu LI
Author Information
1. Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis;
drug effects;
Bone Marrow Cells;
cytology;
Cell Hypoxia;
Cell Survival;
drug effects;
Cells, Cultured;
Culture Media, Serum-Free;
Cysteine Proteinase Inhibitors;
pharmacology;
Female;
Interleukin-10;
secretion;
Leupeptins;
pharmacology;
Male;
Mesenchymal Stromal Cells;
cytology;
Rats;
Rats, Sprague-Dawley
- From:
Acta Physiologica Sinica
2011;63(6):525-532
- CountryChina
- Language:Chinese
-
Abstract:
Bone marrow-derived mesenchymal stem cells (MSCs) have emerged as attractive candidates for cellular therapies for heart and other organ-system disorders. However, a major dilemma in stem cell therapy for ischemic heart diseases is the low survival of transplanted cells in the ischemic and peri-infarcted region. In this study, MSCs were treated by hypoxia and serum deprivation (H/SD) to mimic the ischemic microenvironment of infarcted hearts where MSCs were transplanted. The effects of proteasome inhibitor MG-132 on H/SD-induced apoptosis and paracrine effects were investigated. Apoptosis of MSCs was detected by Annexin V-FITC flow cytometric analysis. Transcriptional levels of IL-1β, TNF-α and IL-10 were examined by real-time PCR. The nuclear translocation of NF-κBp65 was assessed by immunocytochemical staining. Translational changes of IL-1β and TNF-α were detected by Western blot. The secretion of IL-10 from MSCs was examined by ELISA assay. The results showed that MG-132 could effectively suppress H/SD-induced MSCs apoptosis. Furthermore, the induced IL-1β and TNF-α transcription was also inhibited by MG-132 treatment, which may be due to the inhibition of NF-κBp65 nuclear translocation by MG-132. Importantly, MG-132 effectively enhanced H/SD-induced transcription and secretion of IL-10, which is an important paracrine factor from MSCs. Our findings suggest that pretreatment of MSCs by MG-132 before cell transplantation may be an effective strategy to improve cell survival and enhance paracrine effects of MSCs.
