TY - JOUR
T1 - Allosteric modulation of Beta1 Integrin function induces lung tissue repair
AU - Aljamal-naylor, Rehab
AU - Wilson, Linda
AU - Mcintyre, Susan
AU - Rossi, Fiona
AU - Harrison, Beth
AU - Marsden, Mark
AU - Harrison, David J.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Molecular Medicine
KW - Pharmacology, Toxicology and Pharmaceutics(all)
KW - Pharmacology (medical)
UR - http://www.hindawi.com/journals/aps/2012/768720/
U2 - 10.1155/2012/768720
DO - 10.1155/2012/768720
M3 - Article
SN - 1687-6334
VL - 2012
JO - Advances in Pharmacological Sciences
JF - Advances in Pharmacological Sciences
M1 - 768720
ER -