Gene expression profiling of Duchenne muscular dystrophy reveals characteristics along disease progression

Tian, Li; Cao, Ji; Deng, Xingqiang; Zhang, C L; Qian, Tong; Song, Xiaoping; Huang, Baoshan

doi:10.4238/2014.february.28.13

Cited by 10 publications

(13 citation statements)

References 36 publications

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“…presymptomatic patients, pro‐inflammatory and pro‐fibrotic cytokines can be elevated independent of the progression of their dystrophic phenotype (Tian et al . ). A positive correlation between histopathology and cytokine levels was observed only in the diaphragm, suggesting that TNF‐α and TGF‐β serve as markers of dystrophy primarily for this muscle.…”

Section: Discussionmentioning

confidence: 97%

“…), have been suggested to be potential targets for further molecular diagnostic tests (Tian et al . ).…”

mentioning

confidence: 97%

“…In addition, calcium homoeostasis pathways, which are differently regulated in presymptomatic and symptomatic DMD patients (Tian et al . ) and have a role in the pathogenesis of mdx mice (Whitehead et al . ), have been suggested to be potential targets for further molecular diagnostic tests (Tian et al .…”

mentioning

confidence: 99%

“…Gene expression profile studies have revealed that most of the secondary pathways of DMD involve inflammatory responses (Tian et al 2014). Inflammation responses in dystrophic muscles contain several types of immune cells that release pro-inflammatory cytokines such as tumour necrosis factor-alpha (Porter et al 2002;Tidball 2005;Hodgetts et al 2006;Villalta et al 2009).…”

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confidence: 99%

“…These pro-inflammatory cytokines activate metalloproteinases, which breakdown the extracellular matrix and promote the production of pro-fibrotic factors, including tumour growth factor-beta, that will further contribute to myonecrosis and fibrotic deposition (Gosselin et al 2004;Li et al 2009). In addition, calcium homoeostasis pathways, which are differently regulated in presymptomatic and symptomatic DMD patients (Tian et al 2014) and have a role in the pathogenesis of mdx mice (Whitehead et al 2006), have been suggested to be potential targets for further molecular diagnostic tests (Tian et al 2014).…”

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confidence: 99%

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Changes in calsequestrin, TNF‐α, TGF‐β and MyoD levels during the progression of skeletal muscle dystrophy in mdx mice: a comparative analysis of the quadriceps, diaphragm and intrinsic laryngeal muscles

Maranhão

Moreira

Maurício

et al. 2015

Int J Experimental Path

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In Duchenne muscular dystrophy (DMD), the search for new biomarkers to follow the evolution of the disease is of fundamental importance in the light of the evolving gene and pharmacological therapies. In addition to the lack of dystrophin, secondary events including changes in calcium levels, inflammation and fibrosis greatly contribute to DMD progression and the molecules involved in these events may represent potential biomarkers. In this study, we performed a comparative evaluation of the progression of dystrophy within muscles that are differently affected by dystrophy (diaphragm; DIA and quadriceps; QDR) or spared (intrinsic laryngeal muscles) using the mdx mice model of DMD. We assessed muscle levels of calsequestrin (calcium-related protein), tumour necrosis factor (TNF-α; pro-inflammatory cytokine), tumour growth factor (TGF-β; pro-fibrotic factor) and MyoD (muscle proliferation) vs. histopathology at early (1 and 4 months of age) and late (9 months of age) stages of dystrophy. Fibrosis was the primary feature in the DIA of mdx mice (9 months: 32% fibrosis), which was greater than in the QDR (9 months: 0.6% fibrosis). Muscle regeneration was the primary feature in the QDR (9 months: 90% of centrally nucleated fibres areas vs. 33% in the DIA). The QDR expressed higher levels of calsequestrin than the DIA. Laryngeal muscles showed normal levels of TNF-α, TGF-β and MyoD. A positive correlation between histopathology and cytokine levels was observed only in the diaphragm, suggesting that TNF-α and TGF-β serve as markers of dystrophy primarily for the diaphragm.

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Section: Discussionmentioning

confidence: 97%

“…), have been suggested to be potential targets for further molecular diagnostic tests (Tian et al . ).…”

mentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Changes in calsequestrin, TNF‐α, TGF‐β and MyoD levels during the progression of skeletal muscle dystrophy in mdx mice: a comparative analysis of the quadriceps, diaphragm and intrinsic laryngeal muscles

Maranhão

Moreira

Maurício

et al. 2015

Int J Experimental Path

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Long‐Term Therapy With Omega‐3 Ameliorates Myonecrosis and Benefits Skeletal Muscle Regeneration in Mdx Mice

Apolinário

Carvalho

Neto

et al. 2015

The Anatomical Record

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In Duchenne muscle dystrophy (DMD) and in the mdx mouse model of DMD, a lack of dystrophin leads to myonecrosis and cardiorespiratory failure. Several lines of evidence suggest a detrimental role of the inflammatory process in the dystrophic process. Previously, we demonstrated that short-term therapy with eicosapentaenoic acid (EPA), at early stages of disease, ameliorated dystrophy progression in the mdx mouse. In the present study, we evaluated the effects of a long-term therapy with omega-3 later in dystrophy progression. Three-month-old mdx mice received omega-3 (300 mg/kg) or vehicle by gavage for 5 months. The quadriceps and diaphragm muscles were removed and processed for histopathology and Western blot. Long-term therapy with omega-3 increased the regulatory protein MyoD and muscle regeneration and reduced markers of inflammation (TNF-a and NF-kB) in both muscles studied. The present study supports the long-term use of omega-3 at later stages of dystrophy as a promising option to be investigated in DMD clinical trials. Anat Rec, 298:1589Rec, 298: -1596Rec, 298: , 2015. V C 2015 Wiley Periodicals, Inc.

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Mutation-independent Proteomic Signatures of Pathological Progression in Murine Models of Duchenne Muscular Dystrophy

Tle.

Johansson

Hanson

et al. 2020

Molecular & Cellular Proteomics

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The absence of the dystrophin protein in Duchenne muscular dystrophy (DMD) results in myofiber fragility and a plethora of downstream secondary pathologies. While a variety of experimental therapies are in development, achieving effective treatments for DMD remains exceptionally challenging, not least because the pathological consequences of dystrophin loss are incompletely understood. Here we have performed proteome profiling in tibialis anterior muscles from two murine DMD models (mdx and mdx52) at three ages (8, 16, and 80 weeks of age), all n=3. High-resolution isoelectric focusing liquid chromatography-tandem mass spectrometry (HiRIEF-LC-MS/MS) was used to quantify the expression of 4,974 proteins across all 27 samples. The two dystrophic models were found to be highly similar, whereas multiple proteins were differentially expressed relative to wild-type (C57BL/6) controls at each age. Furthermore, 1,795 proteins were differentially expressed when samples were pooled across ages and dystrophic strains. These included numerous proteins associated with the extracellular matrix and muscle function which have not been reported previously. Pathway analysis revealed multiple perturbed pathways and predicted upstream regulators which together are indicative of crosstalk between inflammatory, metabolic, and muscle growth pathways (e.g. TNF, INFγ, NF-κB, SIRT1, AMPK, PGC-1α, PPARs, ILK, and AKT/PI3K). Up-regulation of CAV3, MVP and PAK1 protein expression was validated in dystrophic muscle by Western blot. Furthermore, MVP was up-regulated during, but not required for, the differentiation of C2C12 myoblasts suggesting that this protein may affect muscle regeneration. This study provides novel insights into mutation-independent proteomic signatures characteristic of the dystrophic phenotype and its progression with aging.

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Gene expression profiling of Duchenne muscular dystrophy reveals characteristics along disease progression

Cited by 10 publications

References 36 publications

Changes in calsequestrin, TNF‐α, TGF‐β and MyoD levels during the progression of skeletal muscle dystrophy in mdx mice: a comparative analysis of the quadriceps, diaphragm and intrinsic laryngeal muscles

Changes in calsequestrin, TNF‐α, TGF‐β and MyoD levels during the progression of skeletal muscle dystrophy in mdx mice: a comparative analysis of the quadriceps, diaphragm and intrinsic laryngeal muscles

Long‐Term Therapy With Omega‐3 Ameliorates Myonecrosis and Benefits Skeletal Muscle Regeneration in Mdx Mice

Mutation-independent Proteomic Signatures of Pathological Progression in Murine Models of Duchenne Muscular Dystrophy

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