ERK1/2-Dependent Gene Expression Contributing to TGFβ-Induced Lens EMT.

Purpose: This study aims to highlight some of the genes that are differentially regulated by ERK1/2 signaling in TGFβ-induced EMT in lens, and their potential contribution to this pathological process.

Materials And Methods: Rat lens epithelial explants were cultured with or without TGFβ over a 3-day-culture period to induce EMT, in the presence or absence of UO126 (ERK1/2 signaling inhibitor), both prior to TGFβ-treatment, or 24 or 48 hours after TGFβ treatment. Smad2/3-nuclear immunolabeling was used to indicate active TGFβ signaling, and quantitative RT-PCR was used to analyze changes in the different treatment groups in expression of the following representative genes: TGFβ signaling (Smad7, Smurf1, and Rnf111), epithelial markers (Pax6, Cdh1, Zeb1, and Zeb2), cell survival/death regulators (Bcl2, Bax, and Bad) and lens mesenchymal markers (Mmp9, Fn1, and Col1a1), over the 3 days of culture.

ERK1/2 signaling is required for the initiation but not progression of TGFβ-induced lens epithelial to mesenchymal transition (EMT).

Transforming Growth Factor Beta (TGFβ) potently induces lens epithelial to mesenchymal transition (EMT). The resultant mesenchymal cells resemble those found in plaques of human forms of subcapsular cataract. Smad signaling has long been implicated as the sole driving force of TGFβ-mediated activity.

Bone Morphogenetic Protein-7 Suppresses TGFβ2-Induced Epithelial-Mesenchymal Transition in the Lens: Implications for Cataract Prevention.

Purpose: Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a key pathologic mechanism underlying cataract. Two members of the transforming growth factor-β (TGFβ) superfamily, TGFβ and bone morphogenetic protein-7 (BMP-7) have functionally distinct roles in EMT. While TGFβ is a potent inducer of EMT, BMP-7 counteracts the fibrogenic activity of TGFβ.

Negative regulation of TGFβ-induced lens epithelial to mesenchymal transition (EMT) by RTK antagonists.

An eclectic range of ocular growth factors with differing actions are present within the aqueous and vitreous humors that bathe the lens. Growth factors that exert their actions via receptor tyrosine kinases (RTKs), such as FGF, play a normal regulatory role in lens; whereas other factors, such as TGFβ, can lead to an epithelial to mesenchymal transition (EMT) that underlies several forms of cataract. The respective downstream intracellular signaling pathways of these factors are in turn tightly regulated.