Myostatin and activin blockade by engineered follistatin results in hypertrophy and improves dystrophic pathology in mdx mouse more than myostatin blockade alone.
Myostatin and activin blockade by engineered follistatin results in hypertrophy and improves dystrophic pathology in mdx mouse more than myostatin blockade alone.
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DOI：
10.1186/s13395-018-0180-z
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发表时间：
2018-10-27
期刊：
影响因子：
4.9
通讯作者：
Ehmann DE
中科院分区：
文献类型：
--
作者：
Iskenderian A;Liu N;Deng Q;Huang Y;Shen C;Palmieri K;Crooker R;Lundberg D;Kastrapeli N;Pescatore B;Romashko A;Dumas J;Comeau R;Norton A;Pan J;Rong H;Derakhchan K;Ehmann DE
由于其对骨骼肌的强烈肥大作用，肌肉生长抑制素拮抗剂正被开发用于治疗Duchenne肌营养不良症。基因工程卵泡抑素有可能结合肌肉生长抑素拮抗剂的肥大和激活素A拮抗剂的抗炎和抗纤维化作用。给C57BL/6小鼠注射基因工程卵泡抑素4周，测量肌肉质量和肌纤维大小。在MDX模型中，在两项研究中，工程卵泡抑素服用12周，与激活素IIB受体或抗肌肉生长抑素抗体的FC融合进行比较。握力和强直力的功能测量与坏死、炎症和纤维化标志物的组织分析相结合，以评估营养不良病理的改善。在野生型和MDX小鼠中，观察到工程卵泡抑素的肌肉质量和股四头肌纤维大小随剂量增加。在MDX中，握力和强直力的增加与坏死、炎症和纤维化的肌肉标记物的改善相结合。基因工程卵泡抑素对营养不良病理的改善比抗肌生长抑素抗体更大。基因工程卵泡抑素在MDX模型中产生肥大和抗纤维化作用。
Myostatin antagonists are being developed as therapies for Duchenne muscular dystrophy due to their strong hypertrophic effects on skeletal muscle. Engineered follistatin has the potential to combine the hypertrophy of myostatin antagonism with the anti-inflammatory and anti-fibrotic effects of activin A antagonism. Engineered follistatin was administered to C57BL/6 mice for 4 weeks, and muscle mass and myofiber size was measured. In the mdx model, engineered follistatin was dosed for 12 weeks in two studies comparing to an Fc fusion of the activin IIB receptor or an anti-myostatin antibody. Functional measurements of grip strength and tetanic force were combined with tissue analysis for markers of necrosis, inflammation, and fibrosis to evaluate improvement in dystrophic pathology. In wild-type and mdx mice, dose-dependent increases in muscle mass and quadriceps myofiber size were observed for engineered follistatin. In mdx, increases in grip strength and tetanic force were combined with improvements in muscle markers for necrosis, inflammation, and fibrosis. Improvements in dystrophic pathology were greater for engineered follistatin than the anti-myostatin antibody. Engineered follistatin generated hypertrophy and anti-fibrotic effects in the mdx model.
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影响因子：
2.8
作者：
Cohn, Ronald D.;Liang, Hsin-Yueh;Wagner, Kathryn R.
通讯作者：
Wagner, Kathryn R.
DOI：
10.1124/jpet.102.041343
发表时间：
2003-01-01
影响因子：
3.5
作者：
De Luca, A;Pierno, S;Camerino, DC
通讯作者：
Camerino, DC
DOI：
10.1007/978-3-319-27511-6_5
发表时间：
2016-01-01
期刊：
GROWTH FACTORS AND CYTOKINES IN SKELETAL MUSCLE DEVELOPMENT, GROWTH, REGENERATION AND DISEASE
影响因子：
--
作者：
Chen, Justin L.;Colgan, Timothy D.;Harrison, Craig A.
通讯作者：
Harrison, Craig A.
影响因子：
3.4
作者：
Campbell, Craig;Mcmillan, Hugh J.;Attie, Kenneth M.
通讯作者：
Attie, Kenneth M.
DOI：
10.1083/jcb.201510086
发表时间：
2016-04-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Capote J;Kramerova I;Martinez L;Vetrone S;Barton ER;Sweeney HL;Miceli MC;Spencer MJ
通讯作者：
Spencer MJ