Laminin α4 and Integrin α6 Are Upregulated in Regenerating dy/dy Skeletal Muscle: Comparative Expression of Laminin and Integrin Isoforms in Muscles Regenerating after Crush Injury

Sorokin, Lydia; Maley, Moira; Moch, Helga; Mark, Helga von der; Mark, Klaus von der; Cadalbert, Laurence; Karosi, Stefanie; Davies, Marilyn; McGeachie, John K.; Grounds, Miranda D.

doi:10.1006/excr.2000.4842

Cited by 50 publications

(36 citation statements)

References 54 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, overexpression of certain integrins can ameliorate muscular dystrophy in DMD mouse models, 14 and some integrins have increased endogenous expression in dy muscle. 90 That CT carbohydrate overexpression inhibits skeletal muscle pathology in multiple muscular dystrophy models, however, does distinguish it from some other therapeutic approaches. For example, therapies including myostatin inhibition and ADAM12 overexpression were not effective in dy W /dy W muscles, 39,40 despite the fact that they did have a positive impact on mdx muscle pathology.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of the Cytotoxic T Cell (CT) Carbohydrate Inhibits Muscular Dystrophy in the dyW Mouse Model of Congenital Muscular Dystrophy 1A

Chandrasekharan²,

Yoon³

et al. 2007

The American Journal of Pathology

108

View full text Add to dashboard Cite

A number of recent studies have demonstrated therapeutic effects of transgenes on the development of muscle pathology in the mdx mouse model for Duchenne muscular dystrophy, but none have been shown also to be effective in mouse models for laminin ␣2-deficient congenital muscular dystrophy (MDC1A). Here, we show that overexpression of the cytotoxic T cell (CT) GalNAc transferase (Galgt2) is effective in inhibiting the development of muscle pathology in the dy W mouse model of MDC1A, much as we had previously shown in mdx animals. Embryonic overexpression of Galgt2 in skeletal muscles using transgenic mice or postnatal overexpression using adenoassociated virus both reduced the extent of muscle pathology in dy W /dy W skeletal muscle. As with mdx mice, embryonic overexpression of the Galgt2 transgene in dy W /dy W myofibers inhibited muscle growth, whereas postnatal overexpression did not. Both embryonic and postnatal overexpression of Galgt2 in dy W /dy W muscle increased the expression of agrin, a protein that, in recombinant form, has been shown to ameliorate disease, whereas laminin ␣1, another disease modifier, was not expressed. Galgt2 overexpression also stimulated the glycosylation of a glycolipid with the CT carbohydrate, and glycolipids accounted for most of the CT-reactive material in postnatal overexpression experiments. These experiments demonstrate that Galgt2 overexpression is effective in altering disease progression in skeletal muscles of dy W mice and should be considered as a therapeutic target in

show abstract

Section: Discussionmentioning

confidence: 99%

Overexpression of the Cytotoxic T Cell (CT) Carbohydrate Inhibits Muscular Dystrophy in the dyW Mouse Model of Congenital Muscular Dystrophy 1A

Chandrasekharan²,

Yoon³

et al. 2007

The American Journal of Pathology

108

View full text Add to dashboard Cite

show abstract

“…Both extracellular splice variants, however, showed the same binding activity to laminin-2. As the laminin ␣4 chain is only present during muscle development and up-regulated in muscle regeneration (31,61), it is tempting to speculate that X1-or X2-containing ␣ 7 ␤ 1 might have subtly distinct functions in these processes.…”

Section: Integrins In Skeletal Musclementioning

confidence: 99%

Integrins: Redundant or Important Players in Skeletal Muscle?

Mayer

2003

Journal of Biological Chemistry

168

140

View full text Add to dashboard Cite

“…Laminin-8, composed of ␣ 4 , ␤ 1 , and ␥ 1 chains, and laminin-10 (␣ 5 , ␤ 1 , ␥ 1 ), which were originally identified in endothelial cell basement membranes (21,23,24,27), are also expressed in muscle fiber basement membranes during embryogenesis. Both isoforms are down-regulated during development, remaining at the neuromuscular junction in the mature tissues where they combine with laminin ␤ 2 and ␥ 1 chains to form laminin-9 and -11, respectively (21,28). The 200 -240-kDa ␣ 4 chain that forms laminin-8 together with ␤ 1 and ␥ 1 subunits (29) was localized in fetal and newborn neuromuscular junctions and the endoneurium of intramuscular nerves but disappears in mature muscle, whereas it remains in the capillary endothelium (21).…”

mentioning

confidence: 99%

“…Furthermore, laminin ␣ 4 and ␣ 5 chains reappear to compensate for the lack of laminin-2 in basement membranes of newly formed myotubes in focal le-sions in the dy/dy mice (21). Recent data show that laminins-8 and -10 are up-regulated in the basement membranes of newly formed myotubes during regeneration of normal adult muscle (28).…”

mentioning

confidence: 99%

Alternative Splice Variants of α7β1Integrin Selectively Recognize Different Laminin Isoforms

Mark

Williams

Wendler

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The integrin ␣ 7 ␤ 1 occurs in several cytoplasmic (␣ 7A , ␣ 7B ) and extracellular splice variants (␣ 7X1 , ␣ 7X2 ), which are differentially expressed during development of skeletal and heart muscle. The extracellular variants result from the alternative splicing of exons X1 and X2, corresponding to a segment within the putative ligand binding domain. To study the specificity and affinity of the X1/X2 variants to different laminin isoforms, soluble ␣ 7 ␤ 1 complexes were prepared by recombinant coexpression of the extracellular domains of the ␣-and ␤-subunits. The binding of these complexes to purified ligands was measured by solid phase binding assays. Surprisingly, the alternative splice variants revealed different and specific affinities to different laminin isoforms. While the ␣ 7X2 variant bound much more strongly to laminin-1 than the ␣ 7X1 variant, the latter showed a high affinity binding to laminins-8 and -10/11. Laminin-2, the major laminin isoform in skeletal muscle, was recognized by both variants, whereas none of the two variants were able to interact with laminin-5. A specific blocking antibody inhibited the binding of both variants to all laminins tested, indicating the involvement of common epitopes in ␣ 7X1 ␤ 1 and ␣ 7X2 ␤ 1 . Because laminin-8 and -10/11 as well as ␣ 7X1 are expressed in developing skeletal and cardiac muscle, these findings suggest that ␣ 7X1 ␤ 1 may represent a physiological receptor with novel specificities for laminin-8 and -10.

show abstract

Laminin α4 and Integrin α6 Are Upregulated in Regenerating dy/dy Skeletal Muscle: Comparative Expression of Laminin and Integrin Isoforms in Muscles Regenerating after Crush Injury

Cited by 50 publications

References 54 publications

Overexpression of the Cytotoxic T Cell (CT) Carbohydrate Inhibits Muscular Dystrophy in the dyW Mouse Model of Congenital Muscular Dystrophy 1A

Overexpression of the Cytotoxic T Cell (CT) Carbohydrate Inhibits Muscular Dystrophy in the dyW Mouse Model of Congenital Muscular Dystrophy 1A

Integrins: Redundant or Important Players in Skeletal Muscle?

Alternative Splice Variants of α7β1Integrin Selectively Recognize Different Laminin Isoforms

Contact Info

Product

Resources

About