Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy

Sun, Guozhe; Haginoya, Kazuhiro; Wu, Yanling; Chiba, Yutaka; Nakanishi, Tohru; Ônuma, Akira; Sato, Yuko; Takigawa, Masaharu; Iinuma, Kazuie; Tsuchiya, Shigeru

doi:10.1016/j.jns.2007.09.043

Cited by 94 publications

(91 citation statements)

References 44 publications

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“…However, there have been few studies on the function of CTGF in skeletal muscle fibrosis. CTGF is overexpressed in human muscles in diseases such as Duchenne muscular dystrophy, with TGF-β1 upregulation (Sun et al 2008). Maeda et al (2005) showed that CTGF was expressed in L6 rat skeletal myotubes, and could be induced by TGF-β1 in vitro.…”

Section: Discussionmentioning

confidence: 99%

Expression of TGF-<i>β</i>1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice

Liu

Tang

Chen

et al. 2016

Tohoku J. Exp. Med.

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Injury to the recurrent laryngeal nerve often leads to permanent vocal cord paralysis, which has a significant negative impact on the quality of life. Long-term denervation can induce laryngeal muscle fibrosis，which obstructs the muscle recovery after laryngeal reinnervation. However, the mechanisms of fibrosis remain unclear. In this study, we aimed to analyze the changes in the expression of fibrosis-related factors, including transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in denervated skeletal muscles using a mouse model of accessory nerve transection. Because of the small size, we used sternocleidomastoid muscles instead of laryngeal muscles for denervation experiments. Masson's trichrome staining showed that the grade of atrophy and fibrosis of muscles became more severe with time, but showed a plateau at 4 weeks after denervation, followed by a slow decrease. Quantitative assessment and immunohistochemistry showed that TGF-β1 expression peaked at 1 week after denervation (p < 0.05) and was maintained at its high level until 4 weeks. CTGFand α-SMA-positive muscle cells were detected at 1 week after denervation, peaked at 2 weeks (p < 0.05), and remained at high levels with a subsequent slight decrease for 3-4 weeks. These results suggest that TGF-β1 and CTGF may be involved in the process of denervated skeletal muscle fibrosis. They may induce the differentiation of myoblasts into myofibroblasts, as characterized by the activation of α-SMA. These findings may provide insights on key pathological processes in denervated skeletal muscle fibrosis and develop novel therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Expression of TGF-<i>β</i>1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice

Liu

Tang

Chen

et al. 2016

Tohoku J. Exp. Med.

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“…CTGF has three MCAT elements in the proximal promoter which was confirmed by our analysis (supplementary material Table S3). CTGF is highly expressed in dystrophic muscle (Sun et al, 2008) which contains a high proportion of activated and proliferating satellite cells (Pallafacchina et al, 2010). Thus the high expression of CTGF may be due to the high Yap activity in activated satellite cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells

Judson¹,

Tremblay

Knopp

et al. 2012

Journal of Cell Science

167

137

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SummarySatellite cells are the resident stem cells of skeletal muscle. Mitotically quiescent in mature muscle, they can be activated to proliferate and generate myoblasts to supply further myonuclei to hypertrophying or regenerating muscle fibres, or self-renew to maintain the resident stem cell pool. Here, we identify the transcriptional co-factor Yap as a novel regulator of satellite cell fate decisions. Yap expression increases during satellite cell activation and Yap remains highly expressed until after the differentiation versus self-renewal decision is made. Constitutive expression of Yap maintains Pax7 + and MyoD + satellite cells and satellite cell-derived myoblasts, promotes proliferation but prevents differentiation. In contrast, Yap knockdown reduces the proliferation of satellite cell-derived myoblasts by <40%. Consistent with the cellular phenotype, microarrays show that Yap increases expression of genes associated with Yap inhibition, the cell cycle, ribosome biogenesis and that it represses several genes associated with angiotensin signalling. We also identify known regulators of satellite cell function such as BMP4, CD34 and Myf6 (Mrf4) as genes whose expression is dependent on Yap activity. Finally, we confirm in myoblasts that Yap binds to Tead transcription factors and co-activates MCAT elements which are enriched in the proximal promoters of Yap-responsive genes.

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“…Neue molekulare Erkenntnisse weisen auf eine umgestaltende Rolle spezifischer Botenstoffe [5] und Proteinmodifizierungen [6] hin, welche die Fibrose im Muskelgewebe aktiv zu beeinflussen scheinen [4]. Sekundäre myofibrotische Veränderungen sind besonders auffäl-lig bei der X-chromosomalen Muskeldystrophie.…”

Section: Der Pathologe 1 · 2017 21unclassified

Molekulare Pathogenese der Fibrose bei Muskeldystrophie vom Typ Duchenne

Ohlendieck

Swandulla

2017

Pathologe

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Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy

Cited by 94 publications

References 44 publications

Expression of TGF-<i>β</i>1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice

Expression of TGF-<i>β</i>1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice

The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells

Molekulare Pathogenese der Fibrose bei Muskeldystrophie vom Typ Duchenne

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