Laminin-111: A Potential Therapeutic Agent for Duchenne Muscular Dystrophy

Goudenège, Sébastien; Lamarre, Yann; Dumont, Nicolas A.; Rousseau, Joël; Frenette, Jérôme; Skuk, Daniel; Tremblay, Jacques P.

doi:10.1038/mt.2010.165

Cited by 52 publications

(48 citation statements)

References 43 publications

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“…In addition to being a powerful stimulator of myoblast migration and proliferation in vitro , an intramuscular injection of laminin-111 resulted in increased strength and resistance in treated muscles. When laminin-111 was used as a coadjuvant for myoblast transplantation, this protein was found to considerably improve the overall therapeutic outcomes in the mdx mouse model of DMD [358]. These findings indicate that laminin-111 may serve as an unexpected and highly potent therapeutic agent for patients with congenital myopathies, representing a paradigm for the systemic administration of ECM proteins as therapeutics for genetic diseases [357,358].…”

Section: Human Tissue Ecm-based Biomaterialsmentioning

confidence: 99%

Advancing biomaterials of human origin for tissue engineering

Chen

Liu

2016

Progress in Polymer Science

870

490

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Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for restoration. In particular, there is increasing interest in separating ECMs into simplified functional domains and/or biopolymeric assemblies so that these components/constituents can be discretely exploited and manipulated for the production of bioscaffolds and new biomimetic biomaterials. Here, following an overview of tissue auto-/allo-transplantation, we discuss the recent trends and advances as well as the challenges and future directions in the evolution and application of human-derived biomaterials for reconstructive surgery and tissue engineering. In particular, we focus on an exploration of the structural, mechanical, biochemical and biological information present in native human tissue for bioengineering applications and to provide inspiration for the design of future biomaterials.

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Section: Human Tissue Ecm-based Biomaterialsmentioning

confidence: 99%

Advancing biomaterials of human origin for tissue engineering

Chen

Liu

2016

Progress in Polymer Science

870

490

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“…80,81 We have previously demonstrated that transgenic expression of laminin-111 in laminin a2 chain-deficient mice reduces muscular dystrophy and recent reports have identified laminin-111 as a protein therapeutic. [83][84][85] These results suggest that protein substitution therapy could serve as a future treatment of muscular dystrophy. Although promising, further research is required to better understand the molecular basis of laminin-111 protein therapy as transgenic overexpression of laminin-111 in mdx mice had no ameliorating effect on the dystrophic pathology.…”

Section: Laminin-211 Is Required For Muscle Integritymentioning

confidence: 99%

Laminin-211 in skeletal muscle function

Holmberg

Durbeej²

2013

Cell Adhesion & Migration

111

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A chain is no stronger than its weakest link is an old idiom that holds true for muscle biology. As the name implies, skeletal muscle's main function is to move the bones. However, for a muscle to transmit force and withstand the stress that contractions give rise to, it relies on a chain of proteins attaching the cytoskeleton of the muscle fiber to the surrounding extracellular matrix. The importance of this attachment is illustrated by a large number of muscular dystrophies caused by interruption of the cytoskeletal-extracellular matrix interaction. One of the major components of the extracellular matrix is laminin, a heterotrimeric glycoprotein and a major constituent of the basement membrane. It has become increasingly apparent that laminins are involved in a multitude of biological functions, including cell adhesion, differentiation, proliferation, migration and survival. This review will focus on the importance of laminin-211 for normal skeletal muscle function.

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“…Intramuscular injection of laminin-111 improves muscle strength and diminishes pathology in the mdx mouse as well and additionally increases expression of integrin-␣ 7 ␤ 1 , another receptor for laminin (17,34,35). Furthermore, laminin has proved to be an effective adjuvant for myoblast transplantation in the mdx mouse (17), a potential therapy for muscular dystrophy in mice, which has proven unsuccessful in humans.…”

Section: Discussionmentioning

confidence: 97%

“…Recently, laminins, perlecan, and agrin, all ligands of DG, have been investigated as potential therapies for muscular dystrophies (14,16,17,28,34). In some studies, "miniprotein" constructs, containing DG-binding domains fused to other sequences, have used sequences from agrin and perlecan.…”

mentioning

confidence: 99%

Laminin-α₁ LG4–5 domain binding to dystroglycan mediates muscle cell survival, growth, and the AP-1 and NF-κB transcription factors but also has adverse effects

Zhou

Muñoz

Jiang

et al. 2012

American Journal of Physiology-Cell Physiology

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In our previous studies, we showed laminin binds α-dystroglycan in the dystrophin glycoprotein complex and initiates cell signaling pathways. Here, differentiated C2C12 myocytes serve as a model of skeletal muscle. C2C12 cells have a biphasic response to the laminin-α(1) laminin globular (LG) 4-5 domains (1E3) dependent on the concentration used; at low concentrations of 1E3 (<1 μg/ml), myoblast proliferation is increased while higher concentrations (>1 μg/ml) cause apoptosis in myoblasts and differentiated myotubes. This alters the activation of the transcription factors activator protein-1 (AP-1) and NF-κB via laminin-dystrophin glycoprotein complex (DGC)-src-grb2-sos1-Rac1-Pak1-c-jun N-terminal kinase (JNK)p46 and laminin-DGC-Gβγ-phosphatidylinositol 3-kinase (PI3K)-Akt pathways, respectively. A specific antibody against Ser(63) phosphorylated c-jun completely blocks or supershifts the AP-1-DNA binding resulting from laminin binding but only partially blocks or supershifts the AP-1-DNA binding resulting from 1E3. This suggests that AP-1 contains phosphorylated c-jun in the presence of hololaminin but contains a different composition in the presence of 1E3. Nuclear NF-κB was only upregulated by a low concentration of 1E3 and is then diminished by a higher concentration; it also has a biphasic response. Nuclear localization of NF-κB is affected by PI3K/Akt signaling, and DGC associated PI3K activity also shows a biphasic response to 1E3. Furthermore, our data suggest that activation of c-jun N-terminal kinase participates in the cell survival pathway and suggest that NF-κB is involved in both survival and cell death. A model is presented which incorporates these observations.

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Laminin-111: A Potential Therapeutic Agent for Duchenne Muscular Dystrophy

Cited by 52 publications

References 43 publications

Advancing biomaterials of human origin for tissue engineering

Advancing biomaterials of human origin for tissue engineering

Laminin-211 in skeletal muscle function

Laminin-α₁ LG4–5 domain binding to dystroglycan mediates muscle cell survival, growth, and the AP-1 and NF-κB transcription factors but also has adverse effects

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Laminin-111: A Potential Therapeutic Agent for Duchenne Muscular Dystrophy

Cited by 52 publications

References 43 publications

Advancing biomaterials of human origin for tissue engineering

Advancing biomaterials of human origin for tissue engineering

Laminin-211 in skeletal muscle function

Laminin-α1 LG4–5 domain binding to dystroglycan mediates muscle cell survival, growth, and the AP-1 and NF-κB transcription factors but also has adverse effects

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Laminin-α₁ LG4–5 domain binding to dystroglycan mediates muscle cell survival, growth, and the AP-1 and NF-κB transcription factors but also has adverse effects