Prevention of muscle fibrosis and improvement in muscle performance in the mdx mouse by halofuginone

Turgeman, Tidhar; Hagai, Yosey; Huebner, Kyla D.; Jassal, Davinder S.; Anderson, Judy E.; Genin, Olga; Nagler, Arnon; Halevy, Orna; Pines, Mark

doi:10.1016/j.nmd.2008.06.386

Cited by 116 publications

(109 citation statements)

References 43 publications

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“…85 Recently, a marked improvement of muscle performance was measured in both respiratory and cardiac muscles of mdx mice following treatment with halofuginone, a collagen synthesis inhibitor that prevented fibrosis. 86,87 By demonstrating the key role of fibrosis on muscle function alterations in a dystrophic context, these findings support the hypothesis that the major restriction in endomysial expansion observed in the muscles of our treated GRMD dogs might have a direct impact on their walking ability and largely contribute to their clinical stabilization.…”

Section: Discussionsupporting

confidence: 80%

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Rouger

Larcher

Dubreil

et al. 2011

The American Journal of Pathology

100

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Duchenne muscular dystrophy (DMD) is a genetic progressive muscle disease resulting from the lack of dystrophin and without effective treatment. Adult stem cell populations have given new impetus to cellbased therapy of neuromuscular diseases. One of them, muscle-derived stem cells, isolated based on delayed adhesion properties, contributes to injured muscle repair. However, these data were collected in dystrophic mice that exhibit a relatively mild tissue phenotype and clinical features of DMD patients. Here, we characterized canine delayed adherent stem cells and investigated the efficacy of their systemic delivery in the clinically relevant DMD animal model to assess potential therapeutic application in humans. Delayed adherent stem cells, named MuStem cells (muscle stem cells), were isolated from healthy dog muscle using a preplating technique. In vitro, MuStem cells displayed a large expansion capacity, an ability to proliferate in suspension, and a multilineage differentiation potential. Phenotypically, they corresponded to early myogenic progenitors and uncommitted cells. When injected in immunosuppressed dystrophic dogs, they contributed to myofiber regeneration, satellite cell replenishment, and dystrophin expression. Importantly, their systemic delivery resulted in long-term dystrophin expression, muscle damage course limitation with an increased regeneration activity and an interstitial expansion restriction, and persisting stabilization of the dog's clinical status. These results demonstrate that MuStem cells could provide an attractive therapeutic avenue for DMD patients.

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Section: Discussionsupporting

confidence: 80%

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Rouger

Larcher

Dubreil

et al. 2011

The American Journal of Pathology

100

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“…The performance evaluations of the experimental groups were performed on week 0 and 48 h after the last sessions of the OT protocols at the end of weeks 4 and 8, and consisted of the rotarod test (Turgeman et al 2008, Pereira et al 2015a, da Rocha et al 2015b, the ILT (Pereira et al 2012, 2014a,b, 2015a,b, da Rocha et al 2015a, the exhaustive test (Pereira et al 2012, 2014a,b, 2015a,b, da Rocha et al 2015a, and the grip force test (Anderson et al 2004, da Rocha et al 2015a,b, Pereira et al 2015a). On week 0, the experimental groups performed the ILT without inclination.…”

Section: Performance Evaluationsmentioning

confidence: 99%

“…that was reached 300 s later. Mice performed three consecutive trials and the mean time that each rodent was able to stay on the top of the rotarod treadmill was recorded (Turgeman et al 2008). Four hours after the rotarod test, mice performed the ILT (Pereira et al 2015a, da Rocha et al 2015a).…”

Section: Figurementioning

confidence: 99%

Excessive training impairs the insulin signal transduction in mice skeletal muscles

Pereira¹,

Rocha²,

Pinto³

et al. 2016

Journal of Endocrinology

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The main aim of this investigation was to verify the effects of overtraining (OT) on the insulin and inflammatory signaling pathways in mice skeletal muscles. Rodents were divided into control (CT), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR) groups. Rotarod, incremental load, exhaustive, and grip force tests were used to evaluate performance. Thirty-six hours after the grip force test, the extensor digitorum longus (EDL) and soleus were extracted for subsequent protein analyses. The three OT protocols led to similar responses of all performance evaluation tests. The phosphorylation of insulin receptor beta (pIRβ; Tyr), protein kinase B (pAkt; Ser473), and the protein levels of plasma membrane glucose transporter-4 (GLUT4) were lower in the EDL and soleus after the OTR/down protocol and in the soleus after the OTR/up and OTR protocols. While the pIRβ was lower after the OTR/up and OTR protocols, the pAkt was higher after the OTR/up in the EDL. The phosphorylation of IκB kinase alpha and beta (pIKKα/β; Ser180/181), stress-activated protein kinases/Jun amino-terminal kinases (pSAPK-JNK; Thr183/Tyr185), factor nuclear kappa B (pNFκB p65; Ser536), and insulin receptor substrate 1 (pIRS1; Ser307) were higher after the OTR/down protocol, but were not altered after the two other OT protocols. In summary, these data suggest that OT may lead to skeletal muscle insulin signaling pathway impairment, regardless of the predominance of eccentric contractions, although the insulin signal pathway impairment induced in OTR/up and OTR appeared to be muscle fiber-type specific. Journal of Endocrinology

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“…The performance evaluations were done at week 0 and 48 h after the last sessions of the OT protocols at the end of week 10 and consisted of a rotarod test 13,22,24 , the ILT 13,[18][19][20][21][22] , an exhaustive test 13,18-22 and a grip force test 13,[18][19][20][21][22]25 . The description of these tests and their results were made available recently 13 , using the same sample as this study.…”

Section: Running Ot Protocols and Performance Evaluationsmentioning

confidence: 99%

Hypothalamic endoplasmic reticulum stress of overtrained mice after recovery

Pinto

Oliveira

Rocha

et al. 2017

Motriz: rev. educ. fis.

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-Aims: knowing the relationship between endoplasmic reticulum (ER) stress and inflammation and based on the fact that downhill running-based overtraining (OT) model increases hypothalamus levels of some pro-inflammatory cytokines, we verified the effects of three OT protocols on the levels of BiP, pIRE-1 (Ser734), pPERK (Thr981), pelF2alpha (Ser52), ATF-6 and GRP-94 proteins in the mouse hypothalamus after two weeks of recovery. Methods: the mice were randomized into control (CT), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR) groups. After 2-week total recovery period (i.e., week 10), hypothalamus was removed and used for immunoblotting. Results: the OTR/down group exhibited high levels of BiP and ATF6. The other OT protocols showed higher levels of pPERK (Th981) and pelf-2alpha (Ser52) when compared with the CT group. Conclusion: the current results suggest that after a 2-week total recovery period, the overtrained groups increased partially their ER stress protein levels, but without hypothalamic inflammation, which characterizes a physiological condition related to an adaptation mechanism.

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Prevention of muscle fibrosis and improvement in muscle performance in the mdx mouse by halofuginone

Cited by 116 publications

References 43 publications

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Excessive training impairs the insulin signal transduction in mice skeletal muscles

Hypothalamic endoplasmic reticulum stress of overtrained mice after recovery

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