Factors secreted from high glucose treated endothelial cells impair expansion and differentiation of human skeletal muscle satellite cells
Factors secreted from high glucose treated endothelial cells impair expansion and differentiation of human skeletal muscle satellite cells
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DOI：
10.1113/jp278165
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发表时间：
2019-10-01
影响因子：
5.5
通讯作者：
Gavin, Timothy P.
中科院分区：
文献类型：
--
作者：
Kargl, Christopher K.;Nie, Yaohui;Gavin, Timothy P.
关键点细胞通讯发生在内皮细胞和骨骼肌卫星细胞之间，在正常条件下，这两种细胞类型都是促有丝分裂的。骨骼肌萎缩和内皮细胞功能障碍在心血管疾病、II型糖尿病和衰老中同时发生。本研究探讨了如何诱导内皮细胞功能障碍，通过高糖治疗影响生长和分化的人骨骼肌卫星细胞在体外。高糖处理的内皮细胞分泌的因子通过减少增殖和p38丝裂原活化蛋白激酶在致力于肌生成的卫星细胞中的失调而损害卫星细胞的扩增和分化。这些发现强调了内皮细胞在骨骼肌萎缩的发展和病理学中的新的潜在作用，这在患有内皮功能障碍相关病理学的患者中是常见的。内皮细胞（EC）和骨骼肌卫星细胞（MuSC）之间的串扰已被确定为两种细胞类型中细胞功能的重要调节因子。在健康条件下，EC分泌的因子促进MuSC生长和分化。内皮细胞和卫星细胞功能障碍发生在串联在许多疾病状态，但是，没有数据存在检查功能障碍的EC信号对卫星细胞的影响。因此，本研究的目的是评估从高糖（HG）处理的EC分泌的因子对人卫星细胞（HMuSC）的生长和分化的影响，使用条件培养基（CM）细胞培养模型。从人骨骼肌中分离卫星细胞，并在来自正常或HG处理的人脐静脉EC（HUVEC）的CM中生长。在CM中生长的来自HG处理的HUVEC的卫星细胞减少生长（25%）、分化（25%）和肌层融合（35%）。这些反应与HG处理的HUVEC和HG-CM中增加的超氧化物（50%）和炎性细胞因子（25-50%）相关。HG-CM处理的HMuSC的扩增减少由增殖减少驱动。在HG处理HUVECs的CM处理的HMuSC中，成肌分化因子的基因表达和蛋白质含量受损之前，p38丝裂原活化蛋白激酶的磷酸化水平降低。本研究中获得的结果首次表明，HG处理的EC分泌的因子在体外引起人肌肉卫星细胞生长和分化的损伤，突出了内皮细胞健康和分泌作为治疗血管疾病相关的骨骼肌功能障碍的潜在靶点。
Key pointsCellular communication occurs between endothelial cells and skeletal muscle satellite cells and is mitogenic for both cell types under normal conditions. Skeletal muscle atrophy and endothelial cell dysfunction occur in tandem in cardiovascular disease, type II diabetes and ageing. The present study investigated how induction of endothelial cell dysfunction via high glucose treatment impacts growth and differentiation of human skeletal muscle satellite cells in vitro. Secreted factors from high glucose treated endothelial cells impaired satellite cell expansion and differentiation via decreased proliferation and dysregulation of p38 mitogen-activated protein kinase in satellite cells committed to myogenesis. These findings highlight a novel potential role for endothelial cells in the development and pathology of skeletal muscle atrophy, which is common in patients with endothelial dysfunction related pathologies. Cross-talk between endothelial cells (ECs) and skeletal muscle satellite cells (MuSC) has been identified as an important regulator of cellular functions in both cell types. In healthy conditions, EC secreted factors promote MuSC growth and differentiation. Endothelial and satellite cell dysfunction occur in tandem in many disease states; however, no data exist examining the impact of dysfunctional EC signalling on satellite cells. Therefore, the present study aimed to evaluate the effect that factors secreted from high glucose (HG) treated ECs have on the growth and differentiation of human satellite cells (HMuSC) using a conditioned medium (CM) cell culture model. Satellite cells were isolated from human skeletal muscle and grown in CM from normal or HG treated human umbilical vein ECs (HUVECs). Satellite cells grown in CM from HG treated HUVECs reduced growth (25%), differentiation (25%) and myonuclear fusion (35%). These responses were associated with increased superoxide (50%) and inflammatory cytokines (25-50%) in HG treated HUVECs and HG-CM. Decreased expansion of HG-CM treated HMuSCs was driven by a decrease in proliferation. Impaired gene expression and protein content of myogenic differentiation factors were preceded by decreased phosphorylation of p38 mitogen-activated protein kinase in HMuSC treated with CM from HG treated HUVECs. The results obtained in the present study are the first to show that factors secreted from HG treated ECs cause impairments in human muscle satellite cell growth and differentiation in vitro, highlighting endothelial cell health and secretion as a potential target for treating vascular disease-associated skeletal muscle dysfunction.