Skeletal muscle fiber type-specific expressions of mechanosensors integrin-linked kinase, talin, and vinculin and their modulation by loading and environmental conditions in humans

Skeletal muscle fiber type-specific expressions of mechanosensors integrin-linked kinase, talin, and vinculin and their modulation by loading and environmental conditions in humans
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DOI:
10.1096/fj.202101377rr
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发表时间:
2022-08-01
期刊:
影响因子:
4.8
通讯作者:
Suhr, Frank
Suhr, Frank
中科院分区:
生物学2区
文献类型:
--
作者:
Andresen, Bernhard;de Marees, Markus;Suhr, Frank

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机械传感器控制肌肉的完整性,就像在老鼠身上展示的那样。然而,关于机械传感器的分布以及它们对机械负荷和环境条件(低氧)的适应,目前还没有关于人类肌肉的信息。这里,我们假设机械传感器显示纤维类型特定的分布,负载和环境条件具体控制机械传感器。将28名健康男性随机分为常氧组(NM)、常氧组(NI)、中低氧组(HM)和低氧组(HI),每组7人,每组7人。分别于第3次训练后的Pre(T0)、4 h(T1)、24 h(T2)以及第9次训练后的4 h(T3)、24 h(T4)、72 h(T5)进行组织学检查。我们分析了受试者的最大耗氧量(V?O(2)max)、最大功率输出(Pmax)、肌纤维类型和横截面积(Csa)、纤维类型特异性整合素连接激酶(ILK)的定位以及ILK、vinculin和talin的蛋白和基因表达随负荷和环境条件的变化。V?O(2)max在NM和HM增加,Pmax在所有干预下均增加。纤维类型没有改变,而CSA在NI和HI上增加,在HM上减少。ILK表现为2型特异性纤维类型定位。ILK、vinculin和talin蛋白和基因的表达因负荷和环境条件不同而不同。我们的数据表明,机械传感器显示出纤维类型的特定分布,运动强度而不是环境变量会影响它们在人体肌肉中的分布。这些数据是人类肌肉中的第一个此类数据,表明机械传感器以特定纤维类型的分辨率管理机械传感,机械刺激的强度具有重大影响。
Mechanosensors control muscle integrity as demonstrated in mice. However, no information is available in human muscle about the distribution of mechanosensors and their adaptations to mechanical loading and environmental conditions (hypoxia). Here, we hypothesized that mechanosensors show fiber-type-specific distributions and that loading and environmental conditions specifically regulate mechanosensors. We randomly subjected 28 healthy males to one of the following groups (n = 7 each) consisting of nine loading sessions within 3 weeks: normoxia moderate (NM), normoxia intensive (NI), hypoxia moderate (HM), and hypoxia intensive (HI). We took six biopsies: pre (T0), 4 h (T1), and 24 h (T2) after the third as well as 4 h (T3), 24 h (T4), and 72 h (T5) after the ninth training session. We analyzed subjects' maximal oxygen consumption (V?O(2)max), maximal power output (Pmax), muscle fiber types and cross-sectional areas (CSA), fiber-type-specific integrin-linked kinase (ILK) localizations as well as ILK, vinculin and talin protein and gene expressions in dependence on loading and environmental conditions. V?O(2)max increased upon NM and HM, Pmax upon all interventions. Fiber types did not change, whereas CSA increased upon NI and HI, but decreased upon HM. ILK showed a type 2-specific fiber type localization. ILK, vinculin, and talin protein and gene expressions differed depending on loading and environmental conditions. Our data demonstrate that mechanosensors show fiber type-specific distributions and that exercise intensities rather than environmental variables influence their profiles in human muscles. These data are the first of their kind in human muscle and indicate that mechanosensors manage the mechanosensing at a fiber-type-specific resolution and that the intensity of mechanical stimulation has a major impact.