Epo is relevant neither for microvascular formation nor for the new formation and maintenance of mice skeletal muscle fibres in both normoxia and hypoxia.
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-TAg(h)). Histoimmunology, ELISA and real time RT-PCR did not show any muscle fiber atrophy or accumulation of active HIF-1alpha 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.
Hagström
Luciana
L
Laboratoire Réponses Cellulaires et Fonctionnelles à l'Hypoxie, Université Paris 13, EA 2363, 97017 Bobigny, France.
Agbulut
Onnik
O
El-Hasnaoui-Saadani
Raja
R
Marchant
Dominique
D
Favret
Fabrice
F
Richalet
Jean-Paul
JP
Beaudry
Michèle
M
Launay
Thierry
T
D000704:Analysis of Variance; D000818:Animals; D004921:Erythropoietin / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006651:Histocytochemistry; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D055806:Microvessels / Q000254:growth & development / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism; D009133:Muscular Atrophy; D018919:Neovascularization, Physiologic / Q000502:physiology; D017467:Receptors, Erythropoietin / Q000378:metabolism; D012518:Sarcomeres; D018709:Statistics, Nonparametric; D015854:Up-Regulation; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D017467:Receptors, Erythropoietin; D042442:Vascular Endothelial Growth Factors; D004921:Erythropoietin