Cytoglobin Promotes Cardiac Progenitor Cell Survival against Oxidative Stress via the Upregulation of the NFκB/iNOS Signal Pathway and Nitric Oxide Production.
Cytoglobin Promotes Cardiac Progenitor Cell Survival against Oxidative Stress via the Upregulation of the NFκB/iNOS Signal Pathway and Nitric Oxide Production.
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DOI：
10.1038/s41598-017-11342-6
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发表时间：
2017-09-07
影响因子：
4.6
通讯作者：
Cai C
中科院分区：
文献类型：
--
作者：
Zhang S;Li X;Jourd'heuil FL;Qu S;Devejian N;Bennett E;Jourd'heuil D;Cai C
人心肌干/祖细胞(HCPCS)可作为再生医学用于修复心肌梗死。然而，这种方法受到供体细胞存活率低的严重限制。最近的研究表明，哺乳动物的珠蛋白细胞球蛋白(Cygb)调节一氧化氮(NO)代谢和细胞死亡。在本研究中，我们发现了CygB在HCPCS中的表达。通过提高或降低CygB在HCPCs中表达的分子方法，我们发现CygB在氧化应激反应中作为一种促生存因子发挥作用。这与主要的抗氧化系统，如过氧化还蛋白-1，血红素加氧酶-1，以及抗凋亡因子，包括BCL2，BCL-XL和MCL1的上调有关。最重要的是，我们发现，CygB增加了包括iNOS在内的NFкB依赖基因的表达，并且iNOS依赖的NO产生是维持CygB表达的前馈循环所必需的。我们的研究首次描述了珠蛋白在调节HCPC存活中的作用，并建立了对CygB功能的机械性见解。这为探索CygB途径作为分子靶点以提高心脏干/祖细胞治疗缺血性心脏病的有效性提供了理论基础。
Human cardiac stem/progenitor cells (hCPCs) may serve in regenerative medicine to repair the infarcted heart. However, this approach is severely limited by the poor survival of donor cells. Recent studies suggest that the mammalian globin cytoglobin (CYGB) regulates nitric oxide (NO) metabolism and cell death. In the present study, we found that CYGB is expressed in hCPCs. Through molecular approaches aimed at increasing or decreasing CYGB expression in hCPCs, we found that CYGB functions as a pro-survival factor in response to oxidative stress. This was associated with the upregulation of primary antioxidant systems such as peroxiredoxins-1, heme oxygenase-1, and anti-apoptotic factors, including BCL2, BCL-XL, and MCL1. Most significantly, we established that CYGB increased the expression of NFкB-dependent genes including iNOS, and that iNOS-dependent NO production was required for a feedforward loop that maintains CYGB expression. Our study delineates for the first time a role for a globin in regulating hCPC survival and establishes mechanistic insights in the function of CYGB. It provides a rationale for the exploration of the CYGB pathway as a molecular target that can be used to enhance the effectiveness of cardiac stem/progenitor cell therapy for ischemic heart disease.
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影响因子：
37.8
作者：
Bolli R;Tang XL;Sanganalmath SK;Rimoldi O;Mosna F;Abdel-Latif A;Jneid H;Rota M;Leri A;Kajstura J
通讯作者：
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作者：
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作者：
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作者：
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通讯作者：
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作者：
Fordel, Elke;Thijs, Liesbet;Dewilde, Sylvia
通讯作者：
Dewilde, Sylvia