Nuclear localized Akt limits skeletal muscle derived fibrotic signaling.
Nuclear localized Akt limits skeletal muscle derived fibrotic signaling.
复制标题
核定位 Akt 限制骨骼肌衍生的纤维化信号传导。
DOI：
10.1016/j.bbrc.2018.11.202
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发表时间：
2019
影响因子：
3.1
通讯作者：
Neppl,RonaldL
中科院分区：
文献类型：
--
作者：
Guadagnin,Eleonora;Bagchi,Debalina;Sinha,Indranil;Neppl,RonaldL
损伤后骨骼肌再生是一个复杂的多阶段过程，涉及炎症细胞的募集、肌肉驻留成纤维细胞的激活以及激活的成肌细胞分化为肌细胞。这些细胞过程的失调与肌纤维修复无效和导致纤维化的细胞外基质蛋白过度沉积有关。 PI3K/Akt 信号传导是细胞内和细胞间信号的重要整合者，将营养可用性与细胞存活和生长联系起来。骨骼肌中 PI3K/Akt 通路的激活会导致肥大性生长，并逆转与肥胖和高龄相关的身体成分变化。尽管介导这些效应的分子机制尚不完全清楚，但旁分泌信号传导的变化被认为起着关键作用。在这里，我们利用修饰的 RNA 来研究 Akt 瞬时易位到成熟肌管的肌核的生物学作用。使用条件培养基模型系统，我们发现异位肌核 Akt 会抑制响应氧化应激的纤维化旁分泌信号传导，并且增加或恢复肌核 Akt 的干预措施可能会损害纤维化。
Skeletal muscle regeneration following injury is a complex multi-stage process involving the recruitment of inflammatory cells, the activation of muscle resident fibroblasts, and the differentiation of activated myoblasts into myocytes. Dysregulation of these cellular processes is associated with ineffective myofiber repair and excessive deposition of extracellular matrix proteins leading to fibrosis. PI3K/Akt signaling is a critical integrator of intra- and intercellular signals connecting nutrient availability to cell survival and growth. Activation of the PI3K/Akt pathway in skeletal muscle leads to hypertrophic growth and a reversal of the changes in body composition associated with obesity and advanced age. Though the molecular mechanisms mediating these effects are incompletely understood, changes in paracrine signaling are thought to play a key role. Here, we utilized modified RNA to study the biological role of the transient translocation of Akt to the myonuclei of maturing myotubes. Using a conditioned medium model system, we show that ectopic myonuclear Akt suppresses fibrogenic paracrine signaling in response to oxidative stress, and that interventions that increase or restore myonuclear Akt may impair fibrosis.
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影响因子：
5.2
作者：
Sherwood, RI;Christensen, JL;Wagers, AJ
通讯作者：
Wagers, AJ
影响因子：
29
作者：
Izumiya, Yasuhiro;Hopkins, Teresa;Walsh, Kenneth
通讯作者：
Walsh, Kenneth
DOI：
10.1073/pnas.0909570107
发表时间：
2010-03-30
影响因子：
11.1
作者：
Ren, Hongxia;Accili, Domenico;Duan, Cunming
通讯作者：
Duan, Cunming
DOI：
10.1073/pnas.97.7.3028
发表时间：
2000
影响因子：
11.1
作者：
Y. Pekarsky;A. Koval;C. Hallas;R. Bichi;M. Tresini;S. Malstrom;G. Russo;P. Tsichlis;C. Croce
通讯作者：
Y. Pekarsky;A. Koval;C. Hallas;R. Bichi;M. Tresini;S. Malstrom;G. Russo;P. Tsichlis;C. Croce
影响因子：
23.9
作者：
Warren, Luigi;Manos, Philip D.;Ahfeldt, Tim;Loh, Yuin-Han;Li, Hu;Lau, Frank;Ebina, Wataru;Mandal, Pankaj K.;Smith, Zachary D.;Meissner, Alexander;Daley, George Q.;Brack, Andrew S.;Collins, James J.;Cowan, Chad;Schlaeger, Thorsten M.;Rossi, Derrick J.
通讯作者：
Rossi, Derrick J.