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J. Lee, M.-J. Son, C.-K. Joo; The Regulation of Tgf-ß Induced MMP-14 Expression in Lens Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4224.
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TGF-ß is a key regulator of epithelial-mesenchymal transition (EMT) that induced actin rearrangement, ECM accumulation and cell migration in epithelial cells. Among these TGF-ß responses, the cell migration is closely associated with the expression of matrix metalloproteinases (MMPs). Therefore, we determined which of MMPs were regulated by TGF-ß, examined Smad and PI3K/Akt signaling which previously reported to be activated by TGF-ß.
The TGF-ß induced cell migration assay was performed using boyden chamber. And then, we screened the expression of MMPs using Northern blot and Western blot analysis in TGF-ß treated cells. Furthermore, we confirmed this event using the LECs attached to the anterior capsule of patients with nuclear and anterior polar cataract. Next, we examined if the MMP-14 expression by TGF-ß is associated with Smad2/3 and PI3K/Akt by western blot.
Northern and Western analysis was revealed that the expressions of MMP-2, -14 in HLE B3 cells. In cataract model, MMP-14 was up-regulated. Of these MMPs, the expression of MMP-14 was blocked by PI3K inhibitor and dominant negative Smad3, whereas dominant negative Smad2 had no effect in HLE B3 cells.
The cell migration induced by TGF-ß is closely related to the functions of MMPs and the expression of MMP-14 is specifically involved in Smad3 and PI3K/Akt signaling. Herein, we suggest a novel role of Smad3 and PI3K/Akt signaling in the expression of MMP-14 induced by TGF-ß.
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