| 1 | Live cell screening platform identifies PPAR6 as a regulator of cardiomyocyte proliferation and cardiac repair显示文摘Zebrafish 能高效地通过 cardiomyocyte 增长改革他们的心。相反,哺乳动物的 cardiomyocytes 站立即在出生以后增殖,限制出生后的哺乳动物的心的再生能力。因此,如果出生后的 cardiomyocyte 增长的内长的潜力能被提高,它能为心失败病人提供有希望的未来治疗。这里,我们开始系统地识别触发出生后的 cardiomyocyte 增长的小分子。由屏蔽为估计房间周期阶段利用一个基于 Fucci 的系统的化学复合图书馆,我们作为出生后的 cardiomyocyte 增长的 inducer 识别了 carbacyclin。在 vitro, carbacyclin 经由 peroxisome 导致了新生、成年的 mononuclear 老鼠 cardiomyocytes 的增长激活 proliferator 的受体(PPAR )/PDK1/p308Akt/GSK3/-catenin 小径。PPAR 的抑制在 zebrafish 心新生期间减少了 cardiomyocyte 增长。尤其是,象有在在老鼠的心肌的梗塞以后的 PPAR 收缩筋的治疗一样的组成地活跃的 PPAR 的可诱导的 cardiomyocyte 特定的 overexpression 在 cardiomyocytes 导致了房间周期前进,减少了结疤,并且改进了心脏的功能。一起,我们建立了屏蔽系统和礼品的 cardiomyocyte 增长有为心脏的病理的治疗的诺言的一个新 drugable 目标由 cardiomyocyte 损失引起了。 | Ajit Magadum Yishu Ding Lan He Teayoun Kim Mohankrishna Dalvoy Vasudevarao Qinqiang Long Kevin Yang Nadeera Wickramasinghe Harsha V Renikunta Nicole Dubois Gilbert Weidinger Qinglin Yang Felix B Engel | 2017 | Cell Research2017，27，8： | 6 |
| 5 | Wnt/β-catenin signaling in heart regeneration显示文摘The ability to repair damaged or lost tissues varies significantly among vertebrates.The regenerative ability of the heart is clinically very relevant,because adult teleost fish and amphibians can regenerate heart tissue,but we mammals cannot.Interestingly,heart regeneration is possible in neonatal mice,but this ability is lost within 7 days after birth.In zebrafish and neonatal mice,lost cardiomyocytes are regenerated via proliferation of spared,differentiated cardiomyocytes.While some cardiomyocyte turnover occurs in adult mammals,the cardiomyocyte production rate is too low in response to injury to regenerate the heart.Instead,mammalian hearts respond to injury by remodeling of spared tissue,which includes cardiomyocyte hypertrophy.Wnt/β-catenin signaling plays important roles during vertebrate heart development,and it is re-activated in response to cardiac injury.In this review,we discuss the known functions of this signaling pathway in injured hearts,its involvement in cardiac fibrosis and hypertrophy,and potential therapeutic approaches that might promote cardiac repair after injury by modifying Wnt/β-catenin signaling.Regulation of cardiac remodeling by this signaling pathway appears to vary depending on the injury model and the exact stages that have been studied.Thus,conflicting data have been published regarding a potential role of Wnt/β-catenin pathway in promotion of fibrosis and cardiomyocyte hypertrophy.In addition,the Wnt inhibitory secreted Frizzled-related proteins(sFrps)appear to have Wnt-dependent and Wnt-independent roles in the injured heart.Thus,while the exact functions of Wnt/β-catenin pathway activity in response to injury still need to be elucidated in the non-regenerating mammalian heart,but also in regenerating lower vertebrates,manipulation of the pathway is essential for creation of therapeutically useful cardiomyocytes from stem cells in culture.Hopefully,a detailed understanding of the in vivo role of Wnt/β-catenin signaling in injured mammalian and non-mammalian hearts will also contribute to the success of current efforts towards developing regenerative therapies. | Gunes Ozhan Gilbert Weidinger | 2015 | Cell Regeneration2015，4，1： | 0 |
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