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A. L. Grabitz, Y. Wang, M. K. Duncan; Sip-1 is a Factor in Lens Cell Differentiation and EMT after Cataract Surgery. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4769.
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Sip-1, or Smad interacting protein 1, is a member of the Zeb protein family and is a known binding partner of Smad proteins that co-regulate TGFβ induced epithelial-mesenchymal transition (EMT). Sip-1 is critical for the separation of the lens vesicle from the head ectoderm and the later expression of γ-crystallin in lens fibers. This work tests the hypothesis that Sip-1 plays a regulatory role in lens fiber cell differentiation as well as EMT of the lens epithelium in response to cataract surgery.
Mice homozygous for the Sip-1 flox allele were bred with mice carrying the MLR10 Cre gene, which is expressed throughout the lens vesicle. Gene deletion was assessed by immunofluorescent localization of Sip1 and PCR. The structure of lenses lacking Sip1 was assessed by dark field microscopy, whole mount actin imaging and conventional histological methods. C57B6 mice were used as the wild type controls. The potential role of Sip-1 in EMT of lens epithelial cells in response to injury was examined by following Sip-1 expression in the lens epithelium following cataract surgery on living mice.
Wild type mice express endogenous Sip-1 protein throughout the lens vesicle. Later in development Sip-1 expression is maintained in the equatorial lens epithelial cells and newly formed fiber cells, while it drops off in the later stages of fiber cell differentiation. Conditional deletion of Sip-1 at approximately the lens vesicle stage of development results in profound defects in the shape and structure of lens fiber cells leading to opaque lenses that are smaller than normal. Lens fiber cell removal in wild type adult mice results in upregulation of Sip-1 expression in cells undergoing EMT.
These data indicate that Sip-1 is important for lens fiber cell differentiation and suggest a role for the Zeb family members in epithelial-mesenchymal transition after lens injury.
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