Blocking antibodies against integrin-a3, -aM, and -aMß2 de-differentiate myofibroblasts, and improve lung fibrosis and kidney fibrosis
Fibrosis is involved in 45% of deaths in the United States, and no treatment exists to reverse the progression of lung or kidney fibrosis. Myofibroblasts are key to the progression and maintenance of fibrosis. We investigated features of cell adhesion necessary for monocytes to differentiate into myofibroblasts, seeking to identify pathways key to myofibroblast differentiation. Blocking antibodies against integrins a3, aM, and aMß2 de-differentiate myofibroblasts in vitro, lower the pro-fibrotic secretome of myofibroblasts, and treat lung fibrosis and inhibit kidney fibrosis in vivo. Decorin's collagen-binding peptide can be used to direct functionalized blocking antibodies (against integrins-a3, -aM, -aMß2) to both fibrotic lungs and fibrotic kidneys, reducing the dose of antibody necessary to treat fibrosis. This targeted immunotherapy blocking key integrins may be an effective therapeutic for the treatment of fibrosis. Overall design: lung tissue from (1-3) healthy lungs, (4-6) fibrotic lungs, (7-9) fibrotic lungs treated with targeted anti-a3 antibody, and (10-12) fibrotic lungs treated with targeted anti-amb2 antibody were sectioned and processed to isolate the mRNA, then converted to cDNA and sequenced.