Regulation mechanisms of retinal pigment epithelial cell migration by the TGF-beta superfamily.
To investigate the expression of specific receptors, signal transducers and the effect of transforming growth factor-beta (TGF-beta) on retinal pigment epithelium (RPE) migration and proliferation. Human RPE cell line D407 was used in all experiments. The effect of TGF-beta on migration and proliferation were studied using a wound healing model and [3H]-thymidine incorporation, respectively. The expression of RNA related to the TGF-beta superfamily receptors and SMAD1-4 were assayed by reverse transcriptase-polymerase chain reaction (RT-CPR). The effects of TGF-beta on the intracellular position of SMAD were studied by immunoperoxidase and immunofluorescence. Transforming growth factor-beta 4 nm and activin A 0.36 nm stimulated RPE migration. There was no effect on proliferation. RNA for TGF-beta receptors types 1 and 2, and SMAD1-4 were detected in RPE culture. Transforming growth factor-beta signal transducer SMAD2 but not SMAD1 moved from the cytoplasm to the nucleus after TGF-beta stimulation. Transforming growth factor-beta can regulate RPE cell migration through specific signal transduction pathways.