The Center for World Health & Medicine at Saint Louis University (The Center for World Health & Medicine at Saint Louis University)

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疾病领域	数量

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排名前五的药物类型	数量

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天冬氨酸蛋白酶	1

关联

1

项与 The Center for World Health & Medicine at Saint Louis University 相关的药物

CWHM-117

靶点

天冬氨酸蛋白酶

作用机制

天冬氨酸蛋白酶抑制剂

在研机构

The Center for World Health & Medicine at Saint Louis University [+2]

原研机构

中国科学院广州生物医药与健康研究院

在研适应症

疟疾

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

100 项与 The Center for World Health & Medicine at Saint Louis University 相关的临床结果

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0 项与 The Center for World Health & Medicine at Saint Louis University 相关的专利（医药）

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1

项与 The Center for World Health & Medicine at Saint Louis University 相关的文献（医药）

2017-07-01·Molecular Metabolism2区 · 医学

Rev-Erb co-regulates muscle regeneration via tethered interaction with the NF-Y cistrome

2区 · 医学

ArticleOA

作者: Guo, Chun ; Stephens, Natalie A ; Meyers, Marvin J ; Burris, Thomas P ; Sparks, Lauren M ; Smith, Steven R ; Welch, Ryan D ; Sengupta, Monideepa ; Carpenter, Katherine J ; Zhang, Jinsong ; Arnett, Stacy A ; Flaveny, Colin A

OBJECTIVEThe loss of skeletal muscle mass and strength are a central feature of traumatic injury and degenerative myopathies. Unfortunately, pharmacological interventions typically fail to stem the long-term decline in quality of life. Reduced Rev-Erb-mediated gene suppression in cultured C2C12 myoblasts has been shown to stimulate myoblast differentiation. Yet the mechanisms that allow Rev-Erb to pleiotropically inhibit muscle differentiation are not well understood. In this study, we sought to elucidate the role of Rev-Erb in the regulation of muscle differentiation and regeneration in vivo.METHODSUsing Rev-Erbα/β shRNAs, pharmacological ligands, and Rev-Erbα null and heterozygous mice, we probed the mechanism of Rev-Erbα/β regulation of muscle differentiation and muscle regeneration.RESULTSChIP seq analysis of Rev-Erb in differentiating myoblasts showed that Rev-Erbα did not transcriptionally regulate muscle differentiation through cognate Rev-Erb/ROR-response elements but through possible interaction with the cell fate regulator NF-Y at CCAAT-motifs. Muscle differentiation is stimulated by Rev-Erb release from CCAAT-motifs at promoter and enhancer elements of a number of myogenesis proteins. Partial loss of Rev-Erb expression in mice heterozygous for Rev-Erbα accelerated muscle repair in vivo whereas Rev-Erb knockout mice showed deficiencies in regenerative repair compared to wild type mice. These phenotypic differences between heterozygous and knockout mice were not apparently dependent on MRF induction in response to injury. Similarly, pharmacological disruption of Rev-Erb suppressive activity in injured muscle accelerated regenerative repair in response to acute injury.CONCLUSIONSDisrupting Rev-Erb activity in injured muscle accelerates regenerative muscle repair/differentiation through transcriptional de-repression of myogenic programs. Rev-Erb, therefore, may be a potent therapeutic target for a myriad of muscular disorders.

100 项与 The Center for World Health & Medicine at Saint Louis University 相关的药物交易

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100 项与 The Center for World Health & Medicine at Saint Louis University 相关的转化医学

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