Adenoviral-mediated inhibition of connective tissue growth factor in Rat-2 cells.

Connective tissue growth factor (CTGF) is a profibrotic factor shown to induce extracellular matrix production and angiogenesis, two processes involved in the development of diabetic retinopathy (DR). In this study we tested the effect of a recombinant adenovirus encoding for a CTGF antisense oligonucleotide (rAdASO) on the levels of transforming growth factor-beta (TGF-beta) induced expression of CTGF in Rat-2 fibroblasts. Using semi-quantitative RT-PCR, there was a 2-fold increase in CTGF message induced by TGF-beta. Western blot and immunocytochemical analyses revealed a significant increase in CTGF protein level. This upregulation of CTGF by TGF-beta was inhibited by infection with rAdASO. These findings indicate that infection of the Rat-2 cells with rAdASO was effective in decreasing TGF-beta-induced CTGF expression. These results indicate that this viral vector might have therapeutic potential to control elevated CTGF levels that occur in DR.