MG-132 enhances MSCs survival and IL-10 secretion under hypoxia and serum deprivation condition / 生理学报
Acta Physiologica Sinica
;
(6): 525-532, 2011.
Article
in Chinese
| WPRIM
| ID: wpr-335959
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Bone Marrow Cells
/
Cell Hypoxia
/
Cysteine Proteinase Inhibitors
/
Cell Survival
/
Cells, Cultured
/
Interleukin-10
/
Culture Media, Serum-Free
/
Rats, Sprague-Dawley
/
Apoptosis
Limits:
Animals
Language:
Chinese
Journal:
Acta Physiologica Sinica
Year:
2011
Type:
Article
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