First Author | Zhang Y | Year | 2017 |
Journal | Exp Cell Res | Volume | 356 |
Issue | 1 | Pages | 74-84 |
PubMed ID | 28412246 | Mgi Jnum | J:261544 |
Mgi Id | MGI:6151613 | Doi | 10.1016/j.yexcr.2017.04.012 |
Citation | Zhang Y, et al. (2017) Absence of NUCKS augments paracrine effects of mesenchymal stem cells-mediated cardiac protection. Exp Cell Res 356(1):74-84 |
abstractText | Bone marrow-derived mesenchymal stem cells (BM-MSCs) contribute to myocardial repair after myocardial infarction (MI) by secreting a panel of growth factors and cytokines. This study was to investigate the potential mechanisms of the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS) in regulation of the profiles of BM-MSCs secretion and compare the therapeutic efficacy of NUCKS(-/-)- and wide type-BM-MSCs (WT-BM-MSCs) on MI. The secretion profiles between NUCKS(-/-)- and WT-BM-MSCs under hypoxia (1%O2) were analyzed. Gene function analysis showed that compared with WT-BM-MSCs-conditioned medium (CdM), some genes over-presented in NUCKS(-/-)-BM-MSCs-CdM were closely associated with inflammatory response, regulation of cell proliferation, death, migration and secretion. Notably, VEGFa in NUCKS(-/-)-BM-MSCs-CdM was higher than that of WT-BM-MSCs-CdM. WT-BM-MSCs and NUCKS(-/-)-BM-MSCs were transplanted into the peri-infarct region in mice of MI. At 4 weeks after cell transplantation, NUCKS(-/-)- or WT-BM-MSCs group significantly improved heart function and vessels density and reduced infarction size and apoptosis of cardiomyocytes. Furthermore, NUCKS(-/-)-BM-MSCs provided better cardioprotective effects than WT-BM-MSCs against MI. Our study demonstrates that depletion of NUCKS enhances the therapeutic efficacy of BM-MSCs for MI via regulating the secretion. |