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M. Massaro-Giordano, M. Montanari, C. M. Marshall, A. Giordano, M. Macaluso; MAP Kinase Signaling Pathway in Human Corneal and Conjunctival Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4630.
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© ARVO (1962-2015); The Authors (2016-present)
Plasminogen Activator Inhibitor Type 2 (PAI-2) is a multifunctional protein found in various cell types. Previously, we observed a different expression pattern of PAI-2 protein in the epithelium of the cornea compared to conjunctiva and hypothesized a particular role of this inhibitor in regulating cell proliferation and turnover. We suggested that PAI-2 and the retinoblastoma related protein pRb2/p130 may cooperate with specific chromatin remodeling enzymes in modulating PAI-2 transcription, and investigated if transforming growth factor β-1 (TGF-β1) and phorbol 12-myristate 13-acetate (PMA) affect pRb2/p130 and PAI-2 interaction and/or their binding on PAI-2 promoter. We found that TGF-β1 or PMA treatments do not directly affect the interaction of PAI-2 and pRb2/p130 on the PAI-2 promoter. We hypothesize that, in corneal and conjunctival cells, TGF-β1 and PMA treatments indirectly control PAI-2 and pRb2/p130 levels inducing specific cellular signaling, via intracellular routes (MAPK/ERK, PKC) that may regulate the stability and the degradation of PAI-2 protein and/or PAI-2 mRNA.
We determined the expression profile of a panel of genes related to the MAP Kinase (MAPK) signaling pathway including members of the MKKK, MKK, and MAPK families. The array included: activated transcription factor genes whose expression is induced by MAP Kinase signaling, Raf regulating proteins, MEKK1 interacting proteins, PAI-2 protein, pRb family proteins, scaffolding/anchoring proteins and cell cycle proteins regulated by the Erk1/2 pathway. The experiments have been performed in human cornea and conjunctiva primary cell lines, TGF-β1 and PMA treated or untreated, using a Human MAP Kinase Signaling Pathway PCR Array.
By comparing the gene expression profile of cornea and conjunctiva cell lines, we were able to identify differences and similarities in the expression pattern of a set of genes related to MAPK signaling. Our preliminary results showed that a variety of genes have differential expression in our experimental cell lines suggesting that the expression may be cell-type specific.
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