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FJ Lovicu, L Iyengar, OT Lynch, JW McAvoy; MAPK (ERK1/2) Signalling In Growth Factor-induced Lens Cell Proliferation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2351.
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Purpose: A number of different growth factors, including members of the FGF, IGF/insulin and PDGF families, can induce lens epithelial cells to undergo cell division. Recent studies from our laboratory have shown that FGF-induced lens cell proliferation is dependent on activation of the MAPK (ERK1/2) signalling pathway. To determine if IGF and PDGF utilise the same signalling pathway(s) as FGF, we examined the role of ERK1/2 signalling in IGF- and PDGF-induced lens cell proliferation. Methods: Rat lens epithelial explants treated with IGF-1 (50ng/ml) or PDGF-A (10ng/ml) were cultured for either 10 mins, 20 mins, 24 hrs or 48 hrs. Cell proliferation was assayed using immunolabelling for incorporation of BrdU. Activation of ERK1/2 was assayed using western blotting and immunofluorescence with specific antibodies. Blocking experiments using UO126 (a specific inhibitor of ERK1/2 activation) were also used to assess the role of ERK1/2 signalling in IGF- and PDGF-induced lens cell proliferation. In addition, immunofluorescence on frozen tissue sections was used to localise the phosphorylated (active) forms of ERK1/2 in the lens. Results: IGF was shown to induce lens cell proliferation by 1 day of culture, whereas PDGF did not induce cell proliferation until 2 days. This difference can be correlated with differences in the mode that these growth factors activate ERK1/2. IGF induced the activation of ERK1/2 within 20 mins of culture, whereas PDGF-induced ERK1/2 activation was apparent as early as 10 mins, followed by a marked decrease at 20 mins, which still persisted at 48 hours. Our blocking studies showed that activation of ERK is required for both IGF- and PDGF-induced lens cell proliferation. The labelling patterns of activated ERK1/2 in the intact lens are consistent with the results of our in vitro studies. Conclusion: Similar to FGF, both IGF and PDGF can induce lens cell proliferation, in an ERK-dependent fashion. Differences in the temporal activation of lens cell proliferation by IGF and PDGF may be due to differences in the mode by which these growth factors activate ERK1/2. Overall, our results support an important role for ERK signalling in growth factor-induced lens cell proliferation.
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