Increased mitotic rate coincident with transient telomere lengthening resulting from pim-1 overexpression in cardiac progenitor cells.
Increased mitotic rate coincident with transient telomere lengthening resulting from pim-1 overexpression in cardiac progenitor cells.
复制标题
DOI：
10.1002/stem.1211
复制
发表时间：
2012-11
期刊：
影响因子：
5.2
通讯作者：
Sussman, Mark A.
中科院分区：
文献类型：
--
作者：
Cottage, Christopher T.;Neidig, Lauren;Sundararaman, Balaji;Din, Shabana;Joyo, Anya Y.;Bailey, Brandi;Gude, Natalie;Hariharan, Nirmala;Sussman, Mark A.
心肌梗死后的心脏再生取决于c-kit+心脏前体细胞(CPC)再生受损心肌的能力。CPC重建心脏的能力受到患者年龄和疾病进展的限制。增加CPC的增殖、端粒长度和存活率将提高自体CPC在心肌再生中的成功能力。先前的研究表明，通过工程CPC来表达Pim-1激酶可以促进心肌再生，但Pim-1对CPC的细胞和分子机制尚不清楚。我们发现随着心肌保护激酶Pim-1(CPCeP)的过度表达，CPC迅速扩张，然而，有丝分裂比率的增加是短暂的，因为晚期CPCeP的增殖类似于对照CPC。Pim-1修饰CPCeP后，观察到与年轻表型一致的端粒延长；此外，端粒延长与端粒酶表达和活性的增加相一致。有趣的是，端粒长度和端粒酶活性在几轮传代后恢复正常，这与Pim-1在不导致致癌转化的情况下瞬时增加有丝分裂的能力一致。在不永生化的情况下加速CPCeP的有丝分裂是扩大CPCeP群体以提高其治疗效果的一种新策略。干细胞2012；30：2512-2522
Cardiac regeneration following myocardial infarction rests with the potential of c-kit+ cardiac progenitor cells (CPCs) to repopulate damaged myocardium. The ability of CPCs to reconstitute the heart is restricted by patient age and disease progression. Increasing CPC proliferation, telomere length, and survival will improve the ability of autologous CPCs to be successful in myocardial regeneration. Prior studies have demonstrated enhancement of myocardial regeneration by engineering CPCs to express Pim-1 kinase, but cellular and molecular mechanisms for Pim-1-mediated effects on CPCs remain obscure. We find CPCs rapidly expand following overexpression of cardioprotective kinase Pim-1 (CPCeP), however, increases in mitotic rate are short-lived as late passage CPCePs proliferate similar to control CPCs. Telomere elongation consistent with a young phenotype is observed following Pim-1 modification of CPCeP; in addition, telomere elongation coincides with increased telomerase expression and activity. Interestingly, telomere length and telomerase activity normalize after several rounds of passaging, consistent with the ability of Pim-1 to transiently increase mitosis without resultant oncogenic transformation. Accelerating mitosis in CPCeP without immortalization represents a novel strategy to expand the CPC population in order to improve their therapeutic efficacy. Stem Cells2012;30:2512–2522
登录
查看更多内容
影响因子：
56.9
作者：
FENG, JL;FUNK, WD;VILLEPONTEAU, B
通讯作者：
VILLEPONTEAU, B
影响因子：
37.8
作者：
Huang C;Zhang X;Ramil JM;Rikka S;Kim L;Lee Y;Gude NA;Thistlethwaite PA;Sussman MA;Gottlieb RA;Gustafsson AB
通讯作者：
Gustafsson AB
PKC的HTERT磷酸化对于头颈癌细胞中的端粒酶多蛋白完整性和酶活性至关重要。
影响因子：
8.8
作者：
Chang, JT;Lu, YC;Chen, YJ;Tseng, CP;Chen, YL;Fang, CW;Cheng, AJ
通讯作者：
Cheng, AJ
Anthracycline心肌病是通过心脏干细胞池的耗竭介导的，并通过恢复祖细胞功能而挽救。
影响因子：
37.8
作者：
De Angelis A;Piegari E;Cappetta D;Marino L;Filippelli A;Berrino L;Ferreira-Martins J;Zheng H;Hosoda T;Rota M;Urbanek K;Kajstura J;Leri A;Rossi F;Anversa P
通讯作者：
Anversa P
影响因子：
10.5
作者：
Bianchi, Alessandro;Shore, David
通讯作者：
Shore, David