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K. Abe, M. Maeda, K. Sugioka, H. Mishima, Y. Shimomura; Signal Transdution Associated With Collagen Gel Contraction by Corneal Fibroblasts. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2741.
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Transforming growth factor beta (TGF-ß) regulates various cellular functions through several signal transduction pathways including Smad, Rho, and MEK. Tetra peptide TCDL, which is derived from SPARC (secreted protein which is acidic and rich in cysteine), has been reported to inhibit the stimulatory effect of TGF-ß on collagen gel contraction induced by the corneal fibroblasts. However, we have previously found that the Smad pathway does not contribute to the inhibitory effect of TCDL. To understand the underlying mechanism behind the process, we aimed to determine which signal pathway could have been involved in the stimulatory effect of TGF-ß on the collagen gel contraction by the corneal fibroblasts.
Rabbit corneal fibroblasts were embedded in type I collagen gel and were cultured. TGF-ß and one of TCDL (0.3mM), PI3K inhibitor LY294002 (100µM), ROCK/RhoK inhibitor Y-27632 (50µM), and MEK inhibitor PD98059 (100µM) were added to the medium. Subsequently, the diameter of the gel after the 5-day culture and the cell shape in the gel were assessed.
The stimulatory effects of TGF-ß on collagen gel contraction were completely inhibited by TCDL and PI3K inhibitor, and were partially inhibited by Y-27632 and PD98059. The corneal fibroblasts cultured with TCDL or PI3K were seen in a round shape, whereas those cultured with Y-27632 or PD98059 were seen in a spindle shape with some processes.
Our results suggested that PI3K pathway might have been involved in both the effect of TGF-ß on the collagen gel contraction and the inhibitory effect of TCDL on TGF-ß.
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