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TGFß1-Dependent Contraction of Fibroblasts Is Mediated by the PDGF Receptor

From the Department of Ophthalmology, The Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts.

PURPOSE. Contraction of fibroblasts and the resultant tractional force is a contributing factor to fibrotic diseases of the eye, such as proliferative vitreoretinopathy (PVR). Transforming growth factor (TGF)-ß is abundant in the eye, and is one of the growth factors thought to contribute to the development of PVR. A second is platelet-derived growth factor (PDGF). In the current study, the relationship between TGFß1 and PDGF was investigated at the level of cellular contraction.

METHODS. To study cellular contraction, an in vitro type I collagen gel contraction assay was used with a panel of fibroblast lines that expressed the PDGF receptor (PDGFR) or PDGFß receptor (ßPDGFR) or no PDGFRs. The agents tested included rabbit vitreous, TGFß1, and PDGF.

RESULTS. Vitreous promoted cellular contraction, and approximately 60% of this activity was eliminated by preincubation of the vitreous with neutralizing TGFß antibodies. The PDGFR-expressing cells responded better than cells expressing the ßPDGFR or no PDGFRs. Both of the PDGFR-expressing cell lines contracted in response to PDGF, whereas the best response to TGFß1 was observed with cells expressing the PDGFR. Finally, TGFß1 promoted the tyrosine phosphorylation of both of the PDGFRs, and the PDGFR was more strongly phosphorylated than the ßPDGFR.

CONCLUSIONS. The results show that the vitreous promotes cellular contraction, that TGFß is the major factor responsible, and that at least a portion of the TGFß-dependent contraction proceeds through the PDGFR—that is, indirectly. Therefore, the PDGFR is responsible for mediating cellular contraction of multiple growth factors: TGFß and members of the PDGF family.

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