Regulation mechanisms of retinal pigment epithelial cell migration by the TGF-beta superfamily

Purpose: 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.Methods: 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 [H-3]-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.Results: 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.Conclusion: Transforming growth factor-beta can regulate RPE cell migration through specific signal transduction pathways.Universidade Federal de São Paulo, Dept Ophthalmol, BR-04062002 São Paulo, BrazilYamagata Univ, Sch Med, Dept Ophthalmol, Yamagata 99023, JapanUniversidade Federal de São Paulo, Dept Ophthalmol, BR-04062002 São Paulo, BrazilWeb of Scienc