Control of organization and function of muscle and tendon by thrombospondin-4.
Control of organization and function of muscle and tendon by thrombospondin-4.
复制标题
DOI：
10.1016/j.matbio.2014.02.003
复制
发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Stenina-Adognravi O
中科院分区：
文献类型：
--
作者：
Frolova EG;Drazba J;Krukovets I;Kostenko V;Blech L;Harry C;Vasanji A;Drumm C;Sul P;Jenniskens GJ;Plow EF;Stenina-Adognravi O
血小板反应蛋白（TSP）是沉积在细胞外基质中的多功能蛋白质，它们直接影响血管和其他细胞类型的功能。TSP-4是5个TSP家族成员之一，在肌腱和肌肉中大量表达。我们研究了TSP-4缺乏对肌腱胶原和骨骼肌形态和功能的影响。在Thbs 4 −/−小鼠中，肌腱胶原纤维明显大于野生型小鼠，并且在缺陷小鼠中没有TSP-3和TSP-5的代偿性过度表达，这两种TSP与TSP-4同源性最高。TSP-4在骨骼肌中表达，较高水平的TSP-4蛋白与具有高氧化代谢的红色骨骼肌的微血管有关。比目鱼肌内侧（具有主要氧化代谢的红色骨骼肌）中缺乏TSP-4与几种特异性糖胺聚糖修饰水平降低、TGFβ受体β-聚糖表达降低、脂蛋白脂肪酶活性降低（通过与糖胺聚糖结合与血管细胞表面相关）和VLDL摄取降低相关。与野生型小鼠相比，Thbs 4 −/−小鼠的比目鱼肌较小，后肢和前肢握力降低。这些观察结果表明，TSP-4调节ECM沉积、肌腱和肌肉主要部位的组成，而TSP-4的缺乏改变了这些组织的组织、组成和生理功能。
Thrombospondins (TSP) are multifunctional proteins that are deposited in the extracellular matrix where they directly affect the function of vascular and other cell types. TSP-4, one of the 5 TSP family members, is expressed abundantly in tendon and muscle. We have examined the effect of TSP-4 deficiency on tendon collagen and skeletal muscle morphology and function. In Thbs4−/− mice, tendon collagen fibrils are significantly larger than in wild-type mice, and there is no compensatory over-expression of TSP-3 and TSP-5, the two TSPs most highly homologous to TSP-4, in the deficient mice. TSP-4 is expressed in skeletal muscle, and higher levels of TSP-4 protein are associated with the microvasculature of red skeletal muscle with high oxidative metabolism. Lack of TSP-4 in Medial soleus, red skeletal muscle with predominant oxidative metabolism, is associated with decreased levels of several specific glycosaminoglycan modifications, decreased expression of a TGFβ receptor beta-glycan, decreased activity of lipoprotein lipase, which associates with vascular cell surfaces by binding to glycosaminoglycans, and decreased uptake of VLDL. The soleus muscle is smaller and hind- and fore-limb grip strength is reduced in Thbs4−/− mice compared to wild-type mice. These observations suggest that TSP-4 regulates the composition of the ECM at major sites of its deposition, tendon and muscle, and the absence of TSP-4 alters the organization, composition and physiological functions of these tissues.