IGF-1 和肌肉生长抑制素在达乌尔黄鼠（Spermophilus dauricus）不同冬眠阶段骨骼肌和骨中的协同调节。

IGF-1 and myostatin-mediated co-regulation in skeletal muscle and bone of Daurian ground squirrels (Spermophilus dauricus) during different hibernation stages.

机构信息

Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences, Northwest University, Xi'an, 710069, Shaanxi, China; Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an, 710069, Shaanxi, China; Institute of Special Medicine, Shanxi Medical University, Jinzhong, 030619, Shanxi, China.

出版信息

Comp Biochem Physiol A Mol Integr Physiol. 2024 Nov;297:111716. doi: 10.1016/j.cbpa.2024.111716. Epub 2024 Aug 6.

DOI:10.1016/j.cbpa.2024.111716

PMID:39097140

Abstract

Muscle and bone are cooperatively preserved in Daurian ground squirrels (Spermophilus dauricus) during hibernation. As such, we hypothesized that IGF-1 and myostatin may contribute to musculoskeletal maintenance during this period. Thus, we systematically assessed changes in the protein expression levels of IGF-1 and myostatin, as well as their corresponding downstream targets, in the vastus medialis (VM) muscle and femur in Daurian ground squirrels during different stages. Group differences were determined using one-way analysis of variance (ANOVA). Results indicated that the co-localization levels of IGF-1 and its receptor (IGF-1R) increased by 50% during the pre-hibernation period (PRE) and by 35% during re-entry into torpor (RET) compared to the summer active period (SA). The phosphorylation level of FOXO1 in the VM muscle increased by 50% in the torpor (TOR) group and by 82% in the inter-bout arousal (IBA) group compared to the PRE group. The phosphorylation level of SGK-1 increased by 54% in the IBA group and by 62% in the RET group compared to the SA group. In contrast, the protein expression of IGF-1 and phosphorylation levels of PI3K, Akt, mTOR, and GSK3β in the VM muscle showed no obvious differences among the different groups. β-catenin protein expression was up-regulated by 84% in the RET group compared to the SA group, while the content of IGF-1 protein, correlation coefficients of IGF-1 and IGF-1R, and phosphorylation levels of PI3K, Akt, and GSK3β in the femur showed no significant differences among groups. Regarding myostatin and its downstream targets, myostatin protein expression decreased by 70% in the RET group compared to the SA group, whereas ActRIIB protein expression and Smad2/3 phosphorylation in the VM muscle showed no obvious differences among groups. Furthermore, Smad2/3 phosphorylation decreased by 58% in the TOR group and 53% in the RET group compared to the SA group, whereas ActRIIB protein expression in the femur showed no obvious differences among groups. Overall, the observed changes in IGF-1 and myostatin expression and their downstream targets may be involved in musculoskeletal preservation during hibernation in Daurian ground squirrels.

摘要

肌肉和骨骼在达乌尔黄鼠（Spermophilus dauricus）冬眠期间协同保存。因此，我们假设 IGF-1 和肌肉生长抑制素可能有助于在此期间维持肌肉骨骼。因此，我们系统地评估了 IGF-1 和肌肉生长抑制素及其相应下游靶标的蛋白表达水平在达乌尔黄鼠不同阶段的变化。使用单因素方差分析（ANOVA）确定组间差异。结果表明，在预冬眠期（PRE）和重新进入冬眠期（RET）时，IGF-1 及其受体（IGF-1R）的共定位水平分别增加了 50%和 35%，与夏季活跃期（SA）相比。VM 肌肉中的 FOXO1 磷酸化水平在冬眠（TOR）组中增加了 50%，在觉醒间爆发（IBA）组中增加了 82%，与 PRE 组相比。SGK-1 的磷酸化水平在 IBA 组中增加了 54%，在 RET 组中增加了 62%，与 SA 组相比。相比之下，VM 肌肉中的 IGF-1 蛋白表达和磷酸化水平以及 PI3K、Akt、mTOR 和 GSK3β 的磷酸化水平在不同组之间没有明显差异。与 SA 组相比，RET 组的β-catenin 蛋白表达上调了 84%，而股骨中的 IGF-1 蛋白含量、IGF-1 和 IGF-1R 的相关系数以及 PI3K、Akt 和 GSK3β 的磷酸化水平在组间无显著差异。关于肌肉生长抑制素及其下游靶标，RET 组的肌肉生长抑制素蛋白表达与 SA 组相比降低了 70%，而 VM 肌肉中的 ActRIIB 蛋白表达和 Smad2/3 磷酸化水平在组间没有明显差异。此外，TOR 组和 RET 组的 Smad2/3 磷酸化水平与 SA 组相比分别降低了 58%和 53%，而股骨中的 ActRIIB 蛋白表达在组间没有明显差异。总的来说，IGF-1 和肌肉生长抑制素表达及其下游靶标的变化可能参与了达乌尔黄鼠冬眠期间的肌肉骨骼保存。