Short-term exposure to transforming growth factor beta induces long-term fibrotic responses

Wormstone, I. Michael ORCID:, Anderson, Ian K., Eldred, Julie A., Dawes, Lucy J. and Duncan, George (2006) Short-term exposure to transforming growth factor beta induces long-term fibrotic responses. Experimental Eye Research, 83 (5). pp. 1238-1245. ISSN 1096-0007

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Transforming growth factor beta (TGFβ), a potent inducer of cell transdifferentiation, is heavily implicated in fibrotic disorders. Following cataract surgery, aberrant cell growth across the collagenous matrix of the lens capsule leads to fibrosis, and in turn secondary visual loss, known as posterior capsule opacification (PCO). These modifications are associated with transdifferentiated cells. Following surgery, protein levels in the eye transiently increase, lasting a matter of days whereas PCO takes much longer to reach clinical significance. In the present study, a human lens culture model was employed to show that a relatively brief 2-day exposure to TGFβ gives rise to persistent, long-term signalling events resulting 28 days later in matrix contraction and transdifferentiation. These events can be suppressed by application of the human monoclonal anti-TGFβ2 antibody CAT-152 either simultaneously or after TGFβ2 exposure. Radiolabel binding studies revealed the lens capsule serves as a store for TGFβ2. Importantly, similar binding studies showed that the capsule could also serve as a reservoir for CAT-152. The data reveal the longevity of TGFβ2 action through matrix association, but also demonstrate how early application of a TGFβ2 antibody can overcome the detrimental TGFβ actions leading to potential inhibition of PCO development and other fibrotic disorders.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Cells and Tissues
Depositing User: EPrints Services
Date Deposited: 01 Oct 2010 13:38
Last Modified: 03 Jan 2024 02:15
DOI: 10.1016/j.exer.2006.06.013

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