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Yasushi Ikuno, Andrius Kazlauskas; TGFβ1-Dependent Contraction of Fibroblasts Is Mediated by the PDGFα Receptor. Invest. Ophthalmol. Vis. Sci. 2002;43(1):41-46.
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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)-β 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 TGFβ1 and PDGF was investigated at the level of
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 PDGFα receptor (αPDGFR) or PDGFβ receptor
(βPDGFR) or no PDGFRs. The agents tested included rabbit vitreous,
TGFβ1, and PDGF.
results. Vitreous promoted cellular contraction, and approximately 60% of this
activity was eliminated by preincubation of the vitreous with
neutralizing TGFβ antibodies. The αPDGFR-expressing cells responded
better than cells expressing the βPDGFR or no PDGFRs. Both of the
PDGFR-expressing cell lines contracted in response to PDGF, whereas the
best response to TGFβ1 was observed with cells expressing theα
PDGFR. Finally, TGFβ1 promoted the tyrosine phosphorylation of
both of the PDGFRs, and the αPDGFR was more strongly phosphorylated
than the βPDGFR.
conclusions. The results show that the vitreous promotes cellular contraction, that
TGFβ is the major factor responsible, and that at least a portion of
the TGFβ-dependent contraction proceeds through the αPDGFR—that
is, indirectly. Therefore, the αPDGFR is responsible for mediating
cellular contraction of multiple growth factors: TGFβ and members of
the PDGF family.
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