Enhancing Integrin α1 Inserted (I) Domain Affinity to Ligand Potentiates Integrin α1β1-mediated Down-regulation of Collagen Synthesis

Shi, Mingjian; Pedchenko, Vadim; Greer, Briana H.; Horn, Wade D. Van; Santoro, Samuel A.; Sanders, Charles R.; Hudson, Billy G.; Eichman, Brandt F.; Zent, Roy; Pozzi, Ambra

doi:10.1074/jbc.m112.358648

Cited by 24 publications

(17 citation statements)

References 40 publications

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“…In the case of E317A, the perturbations we observed are consistent with a previous study (30). In that case, the authors proposed that E317A represents an activated conformation of ␣1I as the mutation of Glu 317 enhanced signaling as shown by increased ERK activation and down-regulation of collagen synthesis.…”

Section: Discussionsupporting

confidence: 91%

“…The C helix in ␣1I E317A uncoiled as observed in the ␣2I-GFOGER complex, but the displacement of helix 7 did not occur, and the metal ion at the MIDAS of ␣1I E317A was pentacoordinated, whereas the MIDAS in ␣2I-GFOGER was hexacoordinated. More recently, analysis of the solution structure of E317A using NMR (30) showed evidence of significant conformational change in the mutant. In addition, the E317A mutation led to increased binding to collagen and increased activation of the intact ␣1␤1 receptor.…”

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confidence: 99%

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The Structure of Integrin α1I Domain in Complex with a Collagen-mimetic Peptide

Chin¹,

Headey²,

Mohanty

et al. 2013

Journal of Biological Chemistry

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Background: Collagen-binding integrins bind differentially to different types of collagen. Results: The solution structure of integrin ␣1I domain in complex with a collagen-mimetic peptide was determined. Conclusion: Integrin ␣1I domain binds collagen in a distinct orientation compared with ␣2I, but the signal transduction mechanisms appear to be conserved. Significance: Understanding the collagen binding specificity of integrins might enable their selective modulation in disease.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

The Structure of Integrin α1I Domain in Complex with a Collagen-mimetic Peptide

Chin¹,

Headey²,

Mohanty

et al. 2013

Journal of Biological Chemistry

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“…As examples, α 1 β 1-mediated adhesion to collagen has been reported to promote cell proliferation and to impede collagen synthesis as well as suppress remodeling (Riikonen et al 1995, Heino 2000, Shi et al 2012). α 2 β 1-mediated adhesion was shown to inhibit growth of a number of cell types as well as stimulate ECM synthesis and remodeling (Riikonen et al 1995, Heino 2000, Tulla et al 2001, Jokinen et al 2004, Shi et al 2012). Wound contraction processes mediated by adhesion of α 1 β 1 and α 2 β 1 to collagen have been widely reported.…”

Section: Specific Cell Adhesion On the Surface Of Collagen Scaffoldsmentioning

confidence: 99%

Surface biology of collagen scaffold explains blocking of wound contraction and regeneration of skin and peripheral nerves

Yannas¹,

Tzeranis²,

So³

2015

Biomed. Mater.

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We review the details of preparation and of the recently elucidated mechanism of biological (regenerative) activity of a collagen scaffold (dermis regeneration template, DRT) that has induced regeneration of skin and peripheral nerves (PN) in a variety of animal models and in the clinic. DRT is a 3D protein network with optimized pore size in the range 20–125 μm, degradation half-life 14 ± 7 d and ligand densities that exceed 200 μ α1β1 or α2β1 ligands. The pore has been optimized to allow migration of contractile cells (myofibroblasts, MFB) into the scaffold and to provide sufficient specific surface for cell–scaffold interaction; the degradation half-life provides the required time window for satisfactory binding interaction of MFB with the scaffold surface; and the ligand density supplies the appropriate ligands for specific binding of MFB on the scaffold surface. A dramatic change in MFB phenotype takes place following MFB-scaffold binding which has been shown to result in blocking of wound contraction. In both skin wounds and PN wounds the evidence has shown clearly that contraction blocking by DRT is followed by induction of regeneration of nearly perfect organs. The biologically active structure of DRT is required for contraction blocking; well-matched collagen scaffold controls of DRT, with structures that varied from that of DRT, have failed to induce regeneration. Careful processing of collagen scaffolds is required for adequate biological activity of the scaffold surface. The newly understood mechanism provides a relatively complete paradigm of regenerative medicine that can be used to prepare scaffolds that may induce regeneration of other organs in future studies.

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“…Cell transfection. α1KO-Rec CD cells were obtained by transfecting α1KO CD cells (derived from BALB/c mice) with the full-length human integrin α1 subunit cDNA subcloned in pcDNA3.1 vector (Invitrogen) (55). After selection with zeocin (200 μg/ml), integrin α1-expressing cells were selected by fluorescence-activated cell sorting using antibodies recognizing the extracellular I domain of human integrin α1 subunit (TS2/7) (Abcam).…”

Section: Discussionmentioning

confidence: 99%