Allosteric modulation of Beta1 Integrin function induces lung tissue repair
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The cellular cytoskeleton, adhesion receptors, extracellular matrix composition, and their spatial distribution are together fundamental in a cell's balanced mechanical sensing of its environment. We show that, in lung injury, extracellular matrix-integrin interactions are altered and this leads to signalling alteration and mechanical missensing. The missensing, secondary to matrix alteration and cell surface receptor alterations, leads to increased cellular stiffness, injury, and death. We have identified a monoclonal antibody against ?1 integrin which caused matrix remodelling and enhancement of cell survival. The antibody acts as an allosteric dual agonist/antagonist modulator of ?1 integrin. Intriguingly, this antibody reversed both functional and structural tissue injury in an animal model of degenerative disease in lung.
Aljamal-naylor , R , Wilson , L , Mcintyre , S , Rossi , F , Harrison , B , Marsden , M & Harrison , D J 2012 , ' Allosteric modulation of Beta1 Integrin function induces lung tissue repair ' Advances in Pharmacological Sciences , vol 2012 , 768720 . DOI: 10.1155/2012/768720
Advances in Pharmacological Sciences
Copyright © 2012 Rehab AlJamal-Naylor et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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