Transforming growth factor-β1 and fibrosis in congenital muscular dystrophies

Bernasconi, Pia; Blasi, Carlos Hernández; Mora, Marina; Morandi, Lucia; Galbiati, Silvia; Confalonieri, Paolo; Cornelio, F.; Mantegazza, Renato

doi:10.1016/s0960-8966(98)00093-5

Cited by 124 publications

(94 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although TGF-␤, a strong inhibitor of myogenesis (26,27), is present during myogenesis in development or muscle regener- ation, these processes occur successfully (42,43), suggesting that mechanisms to attenuate TGF-␤ signaling might exist. One of these mechanisms could be LRP-1-dependent; we have determined that the amount of LRP-1 decreases substantially during skeletal muscle differentiation (23).…”

Section: Discussionmentioning

confidence: 99%

A Novel Modulatory Mechanism of Transforming Growth Factor-β Signaling through Decorin and LRP-1

Cabello-Verrugio¹,

Brandan

2007

Journal of Biological Chemistry

114

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel Modulatory Mechanism of Transforming Growth Factor-β Signaling through Decorin and LRP-1

Cabello-Verrugio¹,

Brandan

2007

Journal of Biological Chemistry

114

View full text Add to dashboard Cite

show abstract

“…TGF-β is elevated in mdx (12) and DMD muscle (17), especially in the later years of the disease (7). While the specific source of TGF-β is still not known, fibroblasts and leukocytes are likely to be important contributors.…”

Section: Introductionmentioning

confidence: 99%

Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-β

Vetrone¹,

Montecino‐Rodriguez²,

Kudryashova³

et al. 2009

J. Clin. Invest.

265

309

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is an X-linked, degenerative muscle disease that is exacerbated by secondary inflammation. Here, we characterized the immunological milieu of dystrophic muscle in mdx mice, a model of DMD, to identify potential therapeutic targets. We identified a specific subpopulation of cells expressing the Vβ8.1/8.2 TCR that is predominant among TCR-β + T cells. These cells expressed high levels of osteopontin (OPN), a cytokine that promotes immune cell migration and survival. Elevated OPN levels correlated with the dystrophic process, since OPN was substantially elevated in the serum of mdx mice and muscle biopsies after disease onset. Muscle biopsies from individuals with DMD also had elevated OPN levels. To test the role of OPN in mdx muscle, mice lacking both OPN and dystrophin were generated and termed doublemutant mice (DMM mice). Reduced infiltration of NKT-like cells and neutrophils was observed in the muscle of DMM mice, supporting an immunomodulatory role for OPN in mdx muscle. Concomitantly, an increase in CD4 + and FoxP3 + Tregs was also observed in DMM muscle, which also showed reduced levels of TGF-β, a known fibrosis mediator. These inflammatory changes correlated with increased strength and reduced diaphragm and cardiac fibrosis. These studies suggest that OPN may be a promising therapeutic target for reducing inflammation and fibrosis in individuals with DMD.

show abstract

“…In this way, fibrotic scarring ensues, and the regeneration of muscle is precluded by this fibrotic scar. Both TGF-␤ and CTGF are known to be overexpressed in this disease (23,25,26). Moreover, we have previously shown that myoblasts are able to participate in this fibrotic process because they are able not only to produce CTGF but also to respond to the growth factor by increasing ECM production and actin stress fiber formation (27).…”

mentioning

confidence: 98%

Decorin Interacts with Connective Tissue Growth Factor (CTGF)/CCN2 by LRR12 Inhibiting Its Biological Activity

Víal¹,

Gutiérrez²,

Santander

et al. 2011

Journal of Biological Chemistry

105

108

View full text Add to dashboard Cite

Fibrotic disorders are the end point of many chronic diseases in different tissues, where an accumulation of the extracellular matrix occurs, mainly because of the action of the connective tissue growth factor (CTGF/CCN2). Little is known about how this growth factor activity is regulated. We found that decorin null myoblasts are more sensitive to CTGF than wild type myoblasts, as evaluated by the accumulation of fibronectin or collagen III. Decorin added exogenously negatively regulated CTGF pro-fibrotic activity and the induction of actin stress fibers. Using co-immunoprecipitation and in vitro interaction assays, decorin and CTGF were shown to interact in a saturable manner with a K d of 4.4 nM. This interaction requires the core protein of decorin. Experiments using the deletion mutant decorin indicated that the leucine-rich repeats (LRR) 10 -12 are important for the interaction with CTGF and the negative regulation of the cytokine activity, moreover, a peptide derived from the LRR12 was able to inhibit CTGF-decorin complex formation and CTGF activity. Finally, we showed that CTGF specifically induced the synthesis of decorin, suggesting a mechanism of autoregulation. These results suggest that decorin interacts with CTGF and regulates its biological activity.

show abstract

Transforming growth factor-β1 and fibrosis in congenital muscular dystrophies

Cited by 124 publications

References 17 publications

A Novel Modulatory Mechanism of Transforming Growth Factor-β Signaling through Decorin and LRP-1

A Novel Modulatory Mechanism of Transforming Growth Factor-β Signaling through Decorin and LRP-1

Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-β

Decorin Interacts with Connective Tissue Growth Factor (CTGF)/CCN2 by LRR12 Inhibiting Its Biological Activity

Contact Info

Product

Resources

About