title: [MG-132 enhances MSCs survival and IL-10 secretion under hypoxia and serum deprivation condition].
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.
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors.forename: Zong-Wei
authors.initials: ZW
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.forename: Ya-Rui
authors.initials: YR
authors.lastname: Zhao
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Zhuo-Yu
authors.initials: ZY
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016895:Culture Media, Serum-Free; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D016753:Interleukin-10; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde