Syndecan-4 and β1 integrin are regulated by electrical activity in skeletal muscle: Implications for cell adhesion

Ugarte, Gonzalo; Santander, Cristián; Brandan, Enrique

doi:10.1016/j.matbio.2010.03.003

Cited by 10 publications

(8 citation statements)

References 44 publications

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“…Second, as both TSP1 [57] and CD47 [58] can modulate integrin signaling, our data could also reflect changes in cell adhesion as a cause of modifying angiogenesis. Third, weight changes in wild-type and CD47-null mice may represent differences in energy utilization as we previously reported [59]. Weight differences between mouse strains could also be secondary to variation in food intake or activity level, which were not characterized.…”

Section: Discussionmentioning

confidence: 91%

CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis

Ghimire

Yao

Chiba

et al. 2020

Cells

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The aged population is currently at its highest level in human history and is expected to increase further in the coming years. In humans, aging is accompanied by impaired angiogenesis, diminished blood flow and altered metabolism, among others. A cellular mechanism that impinges upon these manifestations of aging can be a suitable target for therapeutic intervention. Here we identify cell surface receptor CD47 as a novel age-sensitive driver of vascular and metabolic dysfunction. With the natural aging process, CD47 and its ligand thrombospondin-1 were increased, concurrent with a reduction of self-renewal transcription factors OCT4, SOX2, KLF4 and cMYC (OSKM) in arteries from aged wild-type mice and older human subjects compared to younger controls. These perturbations were prevented in arteries from aged CD47-null mice. Arterial endothelial cells isolated from aged wild-type mice displayed cellular exhaustion with decreased proliferation, migration and tube formation compared to cells from aged CD47-null mice. CD47 suppressed ex vivo sprouting, in vivo angiogenesis and skeletal muscle blood flow in aged wild-type mice. Treatment of arteries from older humans with a CD47 blocking antibody mitigated the age-related deterioration in angiogenesis. Finally, aged CD47-null mice were resistant to age- and diet-associated weight gain, glucose intolerance and insulin desensitization. These results indicate that the CD47-mediated signaling maladapts during aging to broadly impair endothelial self-renewal, angiogenesis, perfusion and glucose homeostasis. Our findings provide a strong rationale for therapeutically targeting CD47 to minimize these dysfunctions during aging.

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Section: Discussionmentioning

confidence: 91%

CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis

Ghimire

Yao

Chiba

et al. 2020

Cells

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“…Several negative effects can be envisioned as a consequence of this fibrotic phenotype around the skeletal muscle fibres. Individual fibres interact with the surrounding basal lamina through several receptors, such as integrins 29, heparan sulfate proteoglycans 30 and the dystrophin glycoprotein complex (DGC) 31, with functions, among others, of stabilizing muscle cell membranes during cycles of contraction and relaxation. The physical and physiological communication between the ECM constituents and the cell surface receptors would be seriously affected by this excess of abnormal ECM.…”

Section: Discussionmentioning

confidence: 99%

CTGF/CCN‐2 over‐expression can directly induce features of skeletal muscle dystrophy

Morales

Cabello-Verrugio

Santander

et al. 2011

The Journal of Pathology

Self Cite

102

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Muscular dystrophies are diseases characterized by muscle weakness together with cycles of degeneration and regeneration of muscle fibres, resulting in a progressive decrease of muscle mass, diminished muscle force generation and an increase in fibrosis. Fibrotic disorders are the endpoint of many chronic diseases in different tissues, where accumulation of the extracellular matrix (ECM) occurs. Connective tissue growth factor CTGF/CCN2, which is over-expressed in muscular dystrophies, plays a major role in many progressive scarring conditions. To test the hypothesis that CTGF might not only contribute conversion of already damaged muscle into scar tissue, but that it could by itself also directly contribute to skeletal muscle deterioration, we evaluated the effect of CTGF over-expression in tibialis anterior muscle of wild-type mice, using an adenovirus containing the CTGF mouse sequence (Ad-mCTGF). CTGF over-expression induced extensive skeletal muscle damage, which was followed by a massive regeneration of the damaged muscle, as evidenced by increased embryonic myosin and fibres with centrally located nuclei. It also induced strong fibrosis with increased levels of fibronectin, collagen, decorin and α-smooth muscle actin (α-SMA). Moreover, CTGF over-expression caused a decrease of the specific isometric contractile force. Strikingly, when CTGF over-expression stopped, the entire phenotype proved to be reversible, in parallel with normalization of CTGF levels. Thus, CTGF not merely acts downstream of muscle injury but also contributes directly to the deterioration of skeletal muscle phenotype and function. Moreover, normalization of expression levels led to spontaneous reversal of the CTGF-induced phenotype and to full recovery of muscle structure. These observations underscore the importance of CTGF in the pathophysiology of muscular dystrophies and suggest that targeting CTGF might have significant potential in the development of novel therapies for Duchenne muscular dystrophy and related diseases.

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“…Activated integrins, which are connected to the actin cytoskeleton through their intracellular interactors talin and vinculin, cluster along myofiber plasmamembrane and form specialized structures called focal adhesions [ 145 ]. The transmembrane proteoglycan syndecan-4 localizes at costameres as well [ 146 , 147 ] and cooperates with integrins in the assembly of focal adhesions and in cytoskeleton organization [ 148 ]. Of note, syndecan-4 expression is robustly downregulated after 72 h from denervation [ 147 ].…”

Section: Master Regulators Of Muscle Atrophymentioning

confidence: 99%

“…The transmembrane proteoglycan syndecan-4 localizes at costameres as well [ 146 , 147 ] and cooperates with integrins in the assembly of focal adhesions and in cytoskeleton organization [ 148 ]. Of note, syndecan-4 expression is robustly downregulated after 72 h from denervation [ 147 ].…”

Section: Master Regulators Of Muscle Atrophymentioning

confidence: 99%

“…Denervation-induced dysregulation of costamere components may represent an early target. After 3-d denervation, the levels of syndecan-4, a cell surface heparan-sulfate proteoglycan co-operating with integrins and involved in PKC signaling, are reduced [ 147 ]. Accordingly, transcript downregulation of focal adhesion components and ECM receptors was reported after 6-h denervation [ 87 ].…”

Section: Involvement Of Costamere Components In Different Muscle Amentioning

confidence: 99%

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Master Regulators of Muscle Atrophy: Role of Costamere Components

Gorza

Sorge

Seclì

et al. 2021

Cells

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The loss of muscle mass and force characterizes muscle atrophy in several different conditions, which share the expression of atrogenes and the activation of their transcriptional regulators. However, attempts to antagonize muscle atrophy development in different experimental contexts by targeting contributors to the atrogene pathway showed partial effects in most cases. Other master regulators might independently contribute to muscle atrophy, as suggested by our recent evidence about the co-requirement of the muscle-specific chaperone protein melusin to inhibit unloading muscle atrophy development. Furthermore, melusin and other muscle mass regulators, such as nNOS, belong to costameres, the macromolecular complexes that connect sarcolemma to myofibrils and to the extracellular matrix, in correspondence with specific sarcomeric sites. Costameres sense a mechanical load and transduce it both as lateral force and biochemical signals. Recent evidence further broadens this classic view, by revealing the crucial participation of costameres in a sarcolemmal “signaling hub” integrating mechanical and humoral stimuli, where mechanical signals are coupled with insulin and/or insulin-like growth factor stimulation to regulate muscle mass. Therefore, this review aims to enucleate available evidence concerning the early involvement of costamere components and additional putative master regulators in the development of major types of muscle atrophy.

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Syndecan-4 and β1 integrin are regulated by electrical activity in skeletal muscle: Implications for cell adhesion

Cited by 10 publications

References 44 publications

CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis

CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis

CTGF/CCN‐2 over‐expression can directly induce features of skeletal muscle dystrophy

Master Regulators of Muscle Atrophy: Role of Costamere Components

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