Abstract
Erythropoietin (Epo) and vascular growth factor (VEGF) are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Because it has been suggested that Epo could play a role in skeletal muscle development, regeneration, and angiogenesis, we aimed to assess Epo deficiency in both normoxia and hypoxia by using an Epo-deficient transgenic mouse model (Epo-TAgh). Histoimmunology, ELISA and real time RT-PCR did not show any muscle fiber atrophy or accumulation of active HIF-1α but an improvement of microvessel network and an upregulation of VEGFR2 mRNA in Epo-deficient gastrocnemius compared with Wild-Type one. In hypoxia, both models exhibit an upregulation of VEGF120 and VEGFR2 mRNA but no accumulation of Epo protein. EpoR mRNA is not up-regulated in both Epo-deficient and hypoxic gastrocnemius. These results suggest that muscle deconditioning observed in patients suffering from renal failure is not due to Epo deficiency.
Highlights
Erythropoietin (Epo) and vascular growth factor (VEGF) are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions
It has been suggested that Epo could be an important growth factor for skeletal muscle development and repair
Our principal findings are: (1) Epo-deficient anemic muscles do not exhibit atrophy in both normoxia and hypoxia; (2) microvessel network of Epo-deficient mice is improved compared to WT mice; (3) when exposed to hypoxia Epo is not accumulated in hindlimb muscles and both mice linages exhibit an Hypoxia-Inducible Factor-1α (HIF-1α)/100 μg of total protein vascular endothelial growth factor (VEGF) of total protein mRNA HIF-1α/β-actin ratio upregulation of VEGF120 and VEGFR2 in gastrocnemius muscle; (4) EpoR expression is not upregulated by either hypoxia or Epo deficiency
Summary
Erythropoietin (Epo) and vascular growth factor (VEGF) are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Erythropoietin (Epo) is know as a key-regulator of erythropoiesis stimulating proliferation, differentiation, and survival growth of erythroid precursor resulting in the increased production of red blood cells [1] In both men and mice exposed to altitude, plasma Epo concentration reached a peak after a 24-hour period of exposure [2] and subsequently declining in a progressive manner within days or weeks [3, 4]. The injection of recombinant human Epo (rHuEpo) has been shown to improve the regeneration process of rat soleus muscle [9] Taken together, these results suggest a role for Epo on the development and regeneration of skeletal muscle. We may hypothesise that the default of oxygen transport to tissues leads to local hypoxia which induces the accumulation of Hypoxia-Inducible Factor-1α (HIF-1α) and the expression of the angiogenic factor VEGF as shown in anemic brain [13]
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