Absence of NUCKS augments paracrine effects of mesenchymal stem cells-mediated cardiac protection

被引：22

作者：

Zhang, Yuelin ^{[1
]}

Chiu, Sinming ^{[1
]}

Liang, Xiaoting ^{[1
]}

Chai, Yuet-Hung ^{[1
,2
]}

Qin, Yiming ^{[3
]}

Wang, Junwen ^{[4
,5
,6
]}

Li, Xiang ^{[1
]}

Qiu, Beiying ^{[7
]}

Tergaonkar, Vinay ^{[7
]}

Tse, Hung-Fat ^{[1
,2
]}

Lian, Qizhou ^{[1
,2
,3
]}

机构：

[1] Univ Hong Kong, Li Ka Shing Fac Med, Dept Med, Hong Kong, Hong Kong, Peoples R China

[2] Univ Hong Kong, Li Ka Shing Fac Med, Res Ctr Heart Brain Hormone & Hlth Aging, Hong Kong, Hong Kong, Peoples R China

[3] Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China

[4] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ 85259 USA

[5] Mayo Clin, Ctr Individualized Med, Scottsdale, AZ 85259 USA

[6] Arizona State Univ, Dept Biomed Informat, Scottsdale, AZ 85259 USA

[7] Biopolis, Inst Mol & Cellular Biol, Singapore, Singapore

来源：

EXPERIMENTAL CELL RESEARCH | 2017年 / 356卷 / 01期

关键词：

NUCKS; Mesenchymal stem cells; NF-kappa B; Myocardial infarction; NF-KAPPA-B; MYOCARDIAL-INFARCTION; RAT MODEL; HYPOXIA; ACTIVATION; SURVIVAL; HEART; AKT; TRANSPLANTATION; OVEREXPRESSION;

D O I：

10.1016/j.yexcr.2017.04.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 NUCKS4(-/-)- and wide type-BM-MSCs (WT-BM-MSCs) on MI. The secretion profiles between NUCKS-/-- and WT-BM-MSCs under hypoxia (1%O-2) 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 NUCKS4(-/-)-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.

引用

页码：74 / 84

页数：11

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