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Aqueous humour- and growth factor-induced lens cell proliferation is dependent on MAPK/ERK1/2 and Akt/PI3-K signalling
- Source :
-
Experimental Eye Research . Sep2006, Vol. 83 Issue 3, p667-678. 12p. - Publication Year :
- 2006
-
Abstract
- Abstract: The aqueous humour of the eye is a rich source of growth factors, many of which have been shown to be lens cell mitogens; however, the identity of the endogenous mitogen(s) for lens cells is still unknown. As a first approach to identify the mechanisms by which these aqueous humour-derived growth factors induce lens cell proliferation, the present study set out to examine MAPK/ERK1/2 and PI3-K/Akt signalling associated with lens cell proliferation. Using a lens explant system, we examined the effects of different lens mitogens (aqueous humour, FGF, PDGF, IGF and EGF) using 5′–2′-bromo-deoxyuridine incorporation. In addition, we adopted immunolabelling techniques to compare the roles that the ERK1/2 and PI3-K signalling pathways play in regulating lens cell proliferation. We showed that the aqueous humour, and all the other growth factors examined, could activate ERK1/2 and PI3-K/Akt signalling. By targeting these pathways using specific pharmacological inhibitors, we were able to show that both ERK1/2 and PI3-K signalling are required for growth factor-induced lens cell proliferation, and that there was a strong correlation between the spatial distribution of proliferating cells in lens explants with ERK1/2 labelling. Furthermore, our blocking studies confirmed that PI3-K/Akt signalling can act upstream of ERK1/2, potentiating ERK1/2 phosphorylation in growth factor-induced lens cell proliferation. A better understanding of the signalling pathways required for aqueous humour-induced lens cell proliferation may ultimately allow us to identify the mitogen(s) that are important for regulating lens cell proliferation in situ. [Copyright &y& Elsevier]
- Subjects :
- *GROWTH factors
*CELL division
*CYTOKINES
*PEPTIDES
Subjects
Details
- Language :
- English
- ISSN :
- 00144835
- Volume :
- 83
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Experimental Eye Research
- Publication Type :
- Academic Journal
- Accession number :
- 21275387
- Full Text :
- https://doi.org/10.1016/j.exer.2006.03.008