Satellite Cell Ablation Limits Myofiber Regeneration but Not Angiogenesis Following Skeletal Muscle Injury

IF 2 4区 医学 Q3 HEMATOLOGY
Nicole L. Jacobsen, Michael A. Nguyen, Aaron B. Morton, DDW Cornelison, Steven S. Segal
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引用次数: 0

Abstract

Objective

Myotoxin injury of skeletal muscle disrupts myofibers and fragments capillaries. Following injury, myofibers and capillaries regenerate in concert; however, it remains unresolved whether myogenesis and angiogenesis are interdependent processes. We tested the hypothesis that myofiber regeneration is required for revascularization.

Methods

To limit myofiber regeneration, satellite cells were depleted by tamoxifen injections (+TMX) in adult Pax7-CreERT2/+; RosaDTA/+ (Pax7-DTA) mice; vehicle injections (−TMX) served as controls. Two weeks later, the gluteus maximus muscle was injured by local injection of BaCl2. Regeneration of myofibers and microvessels was assessed histologically. Microvascular perfusion was evaluated with fluorescent tracers injected into the bloodstream.

Results

Myofiber regeneration was minimal in +TMX. Through 21 days post injury (dpi), microvascular area (CD31 immunostaining) was similar between +TMX and −TMX, with disoriented microvessels prevailing in +TMX. At 7 dpi, fewer capillaries were perfused in +TMX compared to −TMX. At 21 dpi, EC area and capillary perfusion were not different between groups. For +TMX at 28 dpi, distinct regions with fewer perfused microvessels near “ghost” fibers were accompanied by adjacent areas of robust vascularity and clusters of adipocytes.

Conclusions

Following myotoxin injury after satellite cell ablation, angiogenesis ensues without myogenesis, and the microcirculation remodels according to changes in tissue composition.

卫星细胞消融限制骨骼肌损伤后肌纤维再生,但不限制血管生成
目的肌毒素损伤骨骼肌,破坏肌纤维,破坏毛细血管。损伤后,肌纤维和毛细血管协同再生;然而,肌生成和血管生成是否是相互依赖的过程仍未得到解决。我们验证了肌纤维再生是血运重建所必需的假设。方法:在Pax7-CreERT2/+成人中,他莫昔芬注射(+TMX)耗尽卫星细胞以限制肌纤维再生;RosaDTA/+ (Pax7-DTA)小鼠;车辆注射(−TMX)作为对照。2周后,局部注射BaCl2损伤臀大肌。组织学上评估肌纤维和微血管的再生情况。用荧光示踪剂注入血流评估微血管灌注。结果+TMX组肌纤维再生最小。损伤后21天(dpi), +TMX和- TMX的微血管面积(CD31免疫染色)相似,+TMX以微血管定向紊乱为主。在7 dpi时,与−TMX相比,+TMX的毛细血管灌注较少。21 dpi时,各组间EC面积及毛细血管灌注无显著差异。28 dpi +TMX时,“鬼”纤维附近灌注微血管较少的明显区域伴有邻近血管健全和脂肪细胞聚集的区域。结论卫星细胞消融后肌毒素损伤后,血管生成无肌生成,微循环根据组织组成的变化进行重构。
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来源期刊
Microcirculation
Microcirculation 医学-外周血管病
CiteScore
5.00
自引率
4.20%
发文量
43
审稿时长
6-12 weeks
期刊介绍: The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.
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