Macrophage migration inhibitory factor, MIF, is a cytokine that serves to integrate peripheral and central inflammatory responses. MIF is also a delayed early response gene expressed in non-immune system cells upon growth factor stimulation. Ubiquitous expression and developmental regulation suggest that MIF may have additional roles outside the immune system. We have shown before that MIF expression is strongly correlated with cell differentiation in the developing chicken lens. Furthermore, MIF gene expression in cultured cells is induced by bFGF, a growth factor which is able to induce lens cell differentiation in rat. To examine the possible role of MIF expression in lens-derived cells, we stably transfected rabbit lens-derived epithelial cells (N/N1003A) with a vector allowing constitutive expression of mouse MIF. Microscopic observations revealed major morphological changes in N1003A/MIF cells. The cells increased in size and formed networks of multinucleated fibers and vacuoles. In the intact tissue, lens epithelial cells express the intermediate filament protein, vimentin. Vimentin-positive fibers were observed in N1003A/MIF cells but no positive staining was seen in normal N/N1003A cells. Constitutive expression of MIF is thus associated with changes in both morphology and gene expression in transfected lens-derived cells, suggesting that MIF may have a general role in the differentiation process.
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