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10.1167/iovs.17-21826

http://scihub22266oqcxt.onion/10.1167/iovs.17-21826
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suck abstract from ncbi


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pmid28549095      Invest+Ophthalmol+Vis+Sci 2017 ; 58 (5): 2785-95
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  • KLF4 Plays an Essential Role in Corneal Epithelial Homeostasis by Promoting Epithelial Cell Fate and Suppressing Epithelial?Mesenchymal Transition #MMPMID28549095
  • Tiwari A; Loughner CL; Swamynathan S; Swamynathan SK
  • Invest Ophthalmol Vis Sci 2017[May]; 58 (5): 2785-95 PMID28549095show ga
  • Purpose: The purpose of this study was to test the hypothesis that KLF4 promotes corneal epithelial (CE) cell fate by suppressing the epithelial?mesenchymal transition (EMT), using spatiotemporally regulated CE-specific ablation of Klf4 in Klf4?/?CE (Klf4LoxP/LoxP/Krt12rtTA/rtTA/Tet-O-Cre) mice. Methods: CE-specific ablation of Klf4 was achieved by feeding Klf4?/?CE mice with doxycycline chow. The wild-type (WT; normal chow-fed littermates) and the Klf4?/?CE histology was compared by hematoxylin and eosin?stained sections; EMT marker expression was quantified by quantitative PCR, immunoblots, and immunofluorescent staining; and wound healing rate was measured by CE debridement using Algerbrush. KLF4 and EMT markers were quantified in human corneal limbal epithelial (HCLE) cells undergoing TGF-?1?induced EMT by quantitative PCR, immunoblots, and immunofluorescent staining. Results: The epithelial markers E-cadherin, Krt12, claudin-3, and claudin-4 were down-regulated, whereas the mesenchymal markers vimentin, ?-catenin, survivin, and cyclin-D1 and the EMT transcription factors Snail, Slug, Twist1, Twist2, Zeb1, and Zeb2 were up-regulated in the Klf4?/?CE corneas. The Klf4?/?CE cells migrated faster, filling 93% of the debrided area within 16 hours compared with 61% in the WT. After 7 days of wounding, the Klf4?/?CE cells that filled the gap failed to regain epithelial characteristics, as they displayed abnormal stratification; down-regulation of E-cadherin and Krt12; up-regulation of ?-catenin, survivin, and cyclin-D1; and a 2.5-fold increase in the number of proliferative Ki67+ cells. WT CE cells at the migrating edge and the HCLE cells undergoing TGF-?1?induced EMT displayed significant down-regulation of KLF4. Conclusions: Collectively, these results reveal that KLF4 plays an essential role in CE homeostasis by promoting epithelial cell fate and suppressing EMT.
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