Novel regulatory mechanisms for the proteoglycans decorin and biglycan during muscle formation and muscular dystrophy

Brandan, Enrique; Cabello-Verrugio, Claudio; Víal, Pablo A.

doi:10.1016/j.matbio.2008.07.004

Cited by 84 publications

(91 citation statements)

References 106 publications

(125 reference statements)

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“…In addition, under physiological conditions the release or degradation of these matrisome molecules was reported to contribute to cell signaling through their interactions with cell-surface molecules (45,49,50). Finally, selective degradation of PGs and GPs is known to contribute to cell adhesion and activation of cell proliferation (43,44,51,52).…”

Section: Discussionmentioning

confidence: 99%

Distinct biological events generated by ECM proteolysis by two homologous collagenases

Solomonov

Zehorai

Talmi-Frank

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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It is well established that the expression profiles of multiple and possibly redundant matrix-remodeling proteases (e.g., collagenases) differ strongly in health, disease, and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in vivo activity can lead to extremely diverse tissueremodeling outcomes. We observed that proteolysis of collagen-rich natural extracellular matrix (ECM), performed uniquely by individual homologous proteases, leads to distinct events that eventually affect overall ECM morphology, viscoelastic properties, and molecular composition. We revealed striking differences in the motility and signaling patterns, morphology, and gene-expression profiles of cells interacting with natural collagen-rich ECM degraded by different collagenases. Thus, in contrast to previous notions, matrix-remodeling systems are not redundant and give rise to precise ECM-cell crosstalk. Because ECM proteolysis is an abundant biochemical process that is critical for tissue homoeostasis, these results improve our fundamental understanding its complexity and its impact on cell behavior.T he function and integrity of the extracellular matrix (ECM) is vital for cell behavior as well as for whole-tissue homeostasis (1-4). The ECM undergoes constant remodeling during health and disease states. Its components are regularly being deposited, degraded, or otherwise modified. The highly stable fibrillar collagen type I (Col I) is abundant in many organ-derived ECMs and connective tissues (5, 6); it serves as a tissue scaffold, determining ECM mechanical properties and anchoring other ECM proteins necessary for cell function (7). These processes are orchestrated by multiple remodeling enzymes, among which the matrix metalloproteinase (MMP) family plays an important role. Only a few members of this proteinase family, the collagenases, are able to degrade the resistant fibrillar collagens, i.e., Col I, as well as other ECM molecules (8, 9). The collagenases have conserved amino acids in their zinc-containing catalytic domain (8, 10) and display high structural similarities, as reflected by their functional domain organization. Nevertheless, the complex effects exerted by different MMPs on ECM and cells in vivo remain poorly understood.The enzymatic activity of MMPs, and specifically of collagenases, in vivo is tightly regulated (11), with enzymatic dysregulation causing irreversible damage associated with a variety of diseases. Abnormally elevated levels of MMP-1 or of both MMP-1 and MMP-13 have been associated with different types of cancers and with inflammatory diseases (12-21).Here, we explored the degradation patterns of natural collagenrich ECM by two homologous MMPs and tested the response of cells to intact vs. selectively degraded ECM. We collectively profiled the unique remodeling events caused by two secreted collagenases, MMP-1 and MMP-13, by using biochemical, biophysical, and proteomics tools. We show that these proteases drive morphological, biochemical, and visc...

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Section: Discussionmentioning

confidence: 99%

Distinct biological events generated by ECM proteolysis by two homologous collagenases

Solomonov

Zehorai

Talmi-Frank

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…1,2,5 Decorin-Mediated Neutralization of TGF-␤ A great deal of attention has been focused on the antifibrotic properties of decorin as a neutralizing factor of TGF-␤, and decorin treatment exerts salutary effects in renal disorders involving TGF-␤ overproduction regardless of the mode of decorin administration. 9,21-24 Two decades of investigations confirmed the antifibrotic effects of decorin in several organs, such as kidney, lung, 25 heart, 26 skeletal muscle, 3 liver, 27 blood vessels, 28 skin, 29 and conjunctiva. 30 Several mechanisms of decorin-mediated inactivation of TGF-␤ are postulated, including physical interaction with TGF-␤ and interference with TGF-␤ signaling, either directly or indirectly by regulating other modulators of TGF-␤ activity, particularly fibrillin-1, myostatin, 3,8,[31][32][33] and formation of decorin/TGF-␤ complexes.…”

Section: Decorinmentioning

confidence: 99%

“…9,21-24 Two decades of investigations confirmed the antifibrotic effects of decorin in several organs, such as kidney, lung, 25 heart, 26 skeletal muscle, 3 liver, 27 blood vessels, 28 skin, 29 and conjunctiva. 30 Several mechanisms of decorin-mediated inactivation of TGF-␤ are postulated, including physical interaction with TGF-␤ and interference with TGF-␤ signaling, either directly or indirectly by regulating other modulators of TGF-␤ activity, particularly fibrillin-1, myostatin, 3,8,[31][32][33] and formation of decorin/TGF-␤ complexes. The latter are eliminated from the tissue through the circulation, by urinary excretion, or in the presence of collagen type I sequestration by the ECM ( Figure 1).…”

Section: Decorinmentioning

confidence: 99%

“…[1][2][3][4] They are covalently substituted with a varied number and type of glycosaminoglycan (GAG) side chains, namely chondroitin sulfate (CS), dermatan sulfate (DS), or keratan sulfate (KS). On the basis of the arrangement of the cysteine clusters, ear repeats, intron/ exon organization, and homologies at the protein and genomic levels, the SLRPs are divided into five distinct classes.…”

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confidence: 99%

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Small Leucine-Rich Proteoglycans in Kidney Disease

Schaefer¹

2011

Journal of the American Society of Nephrology

103

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“…27 The relatively small size of the protein core (up to 42 kDa) is another hallmark of this class of proteoglycans, explaining why these compounds are referred to as small leucine-rich proteoglycans. 18,[28][29][30] SLRPs are covalently substituted with glycosaminoglycan (GAG) side chains: chondroitin sulfate, dermatan sulfate or keratan sulfate. The various lengths and states of sulfation contribute to the structural complexity of these molecules.…”

Section: The Family Of Small Leucine-rich Proteoglycansmentioning

confidence: 99%

Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation

2012

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Novel regulatory mechanisms for the proteoglycans decorin and biglycan during muscle formation and muscular dystrophy

Cited by 84 publications

References 106 publications

Distinct biological events generated by ECM proteolysis by two homologous collagenases

Distinct biological events generated by ECM proteolysis by two homologous collagenases

Small Leucine-Rich Proteoglycans in Kidney Disease

Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation

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