Roles of chondroitin sulfate proteoglycan 4 in fibrogenic/adipogenic differentiation in skeletal muscle tissues.
Roles of chondroitin sulfate proteoglycan 4 in fibrogenic/adipogenic differentiation in skeletal muscle tissues.
复制标题
DOI：
10.1016/j.yexcr.2016.08.023
复制
发表时间：
2016-10
影响因子：
3.7
通讯作者：
S. Takeuchi;Shin-ichi Nakano;Katsuyuki Nakamura;Atsufumi Ozoe;P. Chien;Hidehito Yoshihara;F. Hakuno-
中科院分区：
文献类型：
--
作者：
S. Takeuchi;Shin-ichi Nakano;Katsuyuki Nakamura;Atsufumi Ozoe;P. Chien;Hidehito Yoshihara;F. Hakuno-
肌内脂肪组织和纤维组织在某些骨骼肌病理中观察到，如杜氏肌营养不良症和肌肉减少症，并影响肌肉力量和肌生成。它们起源于骨骼肌中常见的纤维化/脂肪形成细胞。因此，阐明纤维形成/脂肪形成细胞分化的调控机制是调节这些疾病的重要一步。以前，我们建立了一个高度成脂祖细胞克隆，2G 11，从大鼠骨骼肌，并表明，碱性成纤维细胞生长因子（bFGF）在这些细胞中是促成脂的。在这里，我们证明了2G 11细胞在转化生长因子（TGF）-β1刺激下产生成纤维细胞，表明它们具有间充质祖细胞（MPC）样特征。先前报道的MPC标志物PDGFRα在其他细胞群中表达。因此，我们生产了特异性结合2G 11细胞表面抗原的单克隆抗体，并鉴定了硫酸软骨素蛋白聚糖4（CSPG 4）作为潜在的MPC标记物。基于RNA干扰分析，我们发现CSPG 4参与bFGF的促脂肪形成作用和TGF-β诱导的α平滑肌肌动蛋白表达和应力纤维形成。通过建立用于MPC检测的额外标志物并表征其在纤维形成/脂肪形成分化中的作用，这些结果将促进骨骼肌病理的有效治疗的发展。
Intramuscular adipose tissue and fibrous tissue are observed in some skeletal muscle pathologies such as Duchenne muscular dystrophy and sarcopenia, and affect muscle strength and myogenesis. They originate from common fibrogenic/adipogenic cells in the skeletal muscle. Thus, elucidating the regulatory mechanisms underlying fibrogenic/adipogenic cell differentiation is an important step toward the mediation of these disorders. Previously, we established a highly adipogenic progenitor clone, 2G11, from rat skeletal muscle and showed that basic fibroblast growth factor (bFGF) is pro-adipogenic in these cells. Here, we demonstrated that 2G11 cells give rise to fibroblasts upon transforming growth factor (TGF)-β1 stimulation, indicating that they possess mesenchymal progenitor cells (MPC)-like characteristics. The previously reported MPC marker PDGFRα is expressed in other cell populations. Accordingly, we produced monoclonal antibodies that specifically bind to 2G11 cell surface antigens and identified chondroitin sulfate proteoglycan 4 (CSPG4) as a potential MPC marker. Based on an RNA interference analysis, we found that CSPG4 is involved in both the pro-adipogenic effect of bFGF and in TGF-β-induced alpha smooth muscle actin expression and stress fiber formation. By establishing an additional marker for MPC detection and characterizing its role in fibrogenic/adipogenic differentiation, these results will facilitate the development of effective treatments for skeletal muscle pathologies.