Erythropoietin reduces the expression of myostatin in mdx dystrophic mice

Abstract

Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. In this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-β1 (TGF-β1), and tumor necrosis factor-α (TNF-α) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO=0.60±0.11, control=1.07±0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-β1 (rhEPO=0.95±0.14, control=1.05±0.16) and TNF-α (rhEPO=0.73±0.20, control=1.01±0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle.

Determination of qPCR Reference Genes Suitable for Normalizing Gene Expression in a Canine Model of Duchenne Muscular Dystrophy

“…As noted above however, our Normfinder analysis tended simply to single out shown ActB to be an exceptionally poor reference gene in cultured differentiating myoblasts derived from healthy and dystrophic mice [27]. Our data here thus supports the hypothesis that ActB is a poor choice of reference gene for muscle-derived samples as a whole (though we also note this gene has been employed as a reference in mdx mice [39]). …”

“…Effective normalization requires appropriate reference genes, and indeed efforts to identify, validate and publicize such genes are becoming more common in a variety of disease states [20][21][22][23][24] and model organisms [25][26][27][28][29][30]. A review of the literature specifically within the DMD field however reveals a considerable number of candidates: selected examples in dystrophic dogs include GAPDH [31][32][33], RPS18 [34], HPRT1 [35,36], 18S [37]; in humans, TBP and GUSB [13]; and in mice GAPDH [33,38], ActB [39], 18S [40]. There appears to be minimal effort to apply reference genes consistently between studies (even varying from manuscript to manuscript within a research group), and data supporting the selection of the gene or genes used is rarely presented.…”

TAK1 inhibition improves myoblast differentiation and alleviates fibrosis in a mouse model of Duchenne muscular dystrophy

“…As a key mediator of fibrosis, fibroblasts are activated by transforming growth factor (TGF)‐β1 during chronic injury 10 . Many studies have shown that TGF‐β1 increases significantly in the muscles of DMD patients, and TGF‐β1 inhibition has been suggested as a potential approach to alleviate fibrosis in DMD 11,12 . However, no effective clinical drugs targeting TGF‐β1 are available to attenuate fibrosis in DMD patients.…”

Evaluation of the gastrointestinal tract in mdx mice: an experimental model of Duchenne muscular dystrophy

“…Among natural rodent and canine animal models of DMD, the mdx mouse model is the most commonly studied . The mdx (X chromosome‐linked muscular dystrophy) mouse originated from spontaneous mutation of the gene . This model is widely used because it is not only genetically uniform but also easy to handle and breed .…”