Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle

Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle
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DOI:
10.1152/japplphysiol.01211.2007
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发表时间:
2008-04-01
影响因子:
3.3
通讯作者:
Pilegaard, Henriette
Pilegaard, Henriette
中科院分区:
医学2区
文献类型:
--
作者:
Lundby, Carsten;Hellsten, Ylva;Pilegaard, Henriette

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研究了人骨骼肌中促红细胞生成素受体(Epo-R)的存在和潜在的生理作用。在这项研究中,我们证明,Epo-R是存在于内皮细胞,平滑肌细胞,和骨骼肌纤维的肌膜的分数。为了研究促红细胞生成素在人骨骼肌中的潜在作用,进行了两项单独的研究:一项研究单次促红细胞生成素注射对骨骼肌基因表达和血浆激素的急性作用,另一项研究长期(14周)促红细胞生成素治疗对骨骼肌结构的作用。受试者(n = 11)接受单次Epo注射15,000 IU(双盲、交叉、安慰剂)。一个单一的Epo注射减少肌红蛋白和增加转铁蛋白受体和MRF-4 mRNA的含量在10小时内注射后。血浆激素保持不变。在接受长期Epo给药的受试者(n = 8)中研究了毛细血管化和纤维肥大,并在前后进行了肌肉活检。Epo治疗没有改变平均纤维面积(0.84 ± 0.2对0.72 ± 0.3 mm(2)),毛细血管/纤维(4.3 ± 0.5对4.4 ± 1.3)或增殖内皮细胞的数量。总之,Epo-R存在于人骨骼肌的血管系统和肌细胞中,表明在这两种细胞类型中起作用。因此,单次注射Epo可调节肌红蛋白、MRF-4和转铁蛋白受体mRNA水平。然而,与我们的假设相反,长期给予Epo对毛细血管化或肌纤维肥大没有明显影响。
The presence and potential physiological role of the erythropoietin receptor (Epo-R) were examined in human skeletal muscle. In this study we demonstrate that Epo-R is present in the endothelium, smooth muscle cells, and in fractions of the sarcolemma of skeletal muscle fibers. To study the potential effects of Epo in human skeletal muscle, two separate studies were conducted: one to study the acute effects of a single Epo injection on skeletal muscle gene expression and plasma hormones and another to study the effects of long-term (14 wk) Epo treatment on skeletal muscle structure. Subjects (n = 11) received a single Epo injection of 15,000 IU (double blinded, cross over, placebo). A single Epo injection reduced myoglobin and increased transferrin receptor and MRF-4 mRNA content within 10 h after injection. Plasma hormones remained unaltered. Capillarization and fiber hypertrophy was studied in subjects (n = 8) who received long-term Epo administration, and muscle biopsies were obtained before and after. Epo treatment did not alter mean fiber area (0.84 +/- 0.2 vs. 0.72 +/- 0.3 mm(2)), capillaries per fiber (4.3 +/- 0.5 vs. 4.4 +/- 1.3), or number of proliferating endothelial cells. In conclusion, the Epo-R is present in the vasculature and myocytes in human skeletal muscle, suggesting a role in both cell types. In accordance, a single injection of Epo regulates myoglobin, MRF-4, and transferrin receptor mRNA levels. However, in contrast to our hypothesis, prolonged Epo administration had no apparent effect on capillarization or muscle fiber hypertrophy.