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信号转导与转录激活因子3信号通路作为治疗肌肉萎缩性疾病的潜在靶点。

Signal transducer and activator of transcription 3 signaling as a potential target to treat muscle wasting diseases.

作者信息

Sala David, Sacco Alessandra

机构信息

Development, Aging and Regeneration Program (DARe), Sanford Burnham Prebys Medical Discovery Institute, San Diego, California, USA.

出版信息

Curr Opin Clin Nutr Metab Care. 2016 May;19(3):171-6. doi: 10.1097/MCO.0000000000000273.

Abstract

PURPOSE OF REVIEW

The review summarizes our current knowledge of the role of signal transducer and activator of transcription 3 (STAT3) signaling in skeletal muscle regeneration and the maintenance of muscle mass.

RECENT FINDINGS

STAT3 signaling plays a pivotal role in regulating the function of multiple cell types in skeletal muscle. This includes muscle stem cells, myofibers, and macrophages. It regulates muscle stem cell function by antagonizing self-renewal. STAT3 also functions in myofibers to regulate skeletal muscle mass. This is highly relevant under pathological conditions where STAT3 activation promotes protein degradation and muscle atrophy. Transient pharmacological inhibition of STAT3 partially prevents muscle wasting. However, the mechanisms responsible for the improvement of muscle condition are not currently well understood. This is because of the complexity of the system, as STAT3 has a critical role in regulating the function of several cell types residing in skeletal muscle.

SUMMARY

Muscle wasting is associated with several human diseases such as muscle dystrophies or cancer cachexia. However, currently there are no effective treatments for this condition, and there is a critical need to identify new potential targets for the development of efficient therapeutic approaches.

摘要

综述目的

本综述总结了我们目前对信号转导和转录激活因子3(STAT3)信号通路在骨骼肌再生和肌肉质量维持中的作用的认识。

最新发现

STAT3信号通路在调节骨骼肌中多种细胞类型的功能方面起着关键作用。这包括肌肉干细胞、肌纤维和巨噬细胞。它通过拮抗自我更新来调节肌肉干细胞功能。STAT3在肌纤维中也发挥作用,以调节骨骼肌质量。在病理条件下,STAT3激活促进蛋白质降解和肌肉萎缩,这一点高度相关。对STAT3进行短暂的药理学抑制可部分预防肌肉萎缩。然而,目前对改善肌肉状况的机制尚不完全清楚。这是由于该系统的复杂性,因为STAT3在调节骨骼肌中多种细胞类型的功能方面起着关键作用。

总结

肌肉萎缩与多种人类疾病相关,如肌肉营养不良或癌症恶病质。然而,目前针对这种情况尚无有效的治疗方法,迫切需要确定新的潜在靶点,以开发有效的治疗方法。

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