The goal of this proposal is to determine the role and regulation of specific adhesion related molecules in the maintenance of corneal epithelial integrity. The cells of the corneal epithelium are tightly adherent to each other as well as to the underlying extracellular matrix. The hypothesis is that transition from the sedentary to migratory state of epithelial cells involves re-distribution, changes in the molecular associations, and post-translational modifications of adhesion related molecules. Upon successful completion of the wound closure, the epithelium would need to reverse the above changes and again establish a stable epithelial configuration. Failures in transitions between sedentary and migratory states of the epithelium, may, in turn, result in inadequate wound healing or unsuccessful re- establishment of sufficient corneal epithelial adhesion following wound closure. Therefore, identifying the molecular determinants of the adhesion state of the corneal epithelium will be crucial to the understanding of adhesion related failures of the epithelium.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007883-10
Application #
2668387
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1988-12-01
Project End
2001-02-28
Budget Start
1998-03-01
Budget End
1999-02-28
Support Year
10
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Florida
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Akin, Debra; Newman, Jeremy R B; McIntyre, Lauren M et al. (2016) RNA-seq analysis of impact of PNN on gene expression and alternative splicing in corneal epithelial cells. Mol Vis 22:40-60
Joo, Jeong Hoon; Ryu, Danny; Peng, Qian et al. (2014) Role of Pnn in alternative splicing of a specific subset of lncRNAs of the corneal epithelium. Mol Vis 20:1629-42
Joo, Jeong-Hoon; Correia, Greg P; Li, Jian-Liang et al. (2013) Transcriptomic analysis of PNN- and ESRP1-regulated alternative pre-mRNA splicing in human corneal epithelial cells. Invest Ophthalmol Vis Sci 54:697-707
Xu, Yufei; Xu, Chao; Kato, Akiko et al. (2012) Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development. Cell 151:1200-13
Joo, Jeong-Hoon; Kim, Yong H; Dunn, Nicholas W et al. (2010) Disruption of mouse corneal epithelial differentiation by conditional inactivation of pnn. Invest Ophthalmol Vis Sci 51:1927-34
Joo, Jeong-Hoon; Taxter, Timothy J; Munguba, Gustavo C et al. (2010) Pinin modulates expression of an intestinal homeobox gene, Cdx2, and plays an essential role for small intestinal morphogenesis. Dev Biol 345:191-203
Alpatov, Roman; Shi, Yujiang; Munguba, Gustavo C et al. (2008) Corepressor CtBP and nuclear speckle protein Pnn/DRS differentially modulate transcription and splicing of the E-cadherin gene. Mol Cell Biol 28:1584-95
Joo, Jeong-Hoon; Lee, Young Jae; Munguba, Gustavo C et al. (2007) Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice. Dev Dyn 236:2147-58
Joo, Jeong-Hoon; Alpatov, Roman; Munguba, Gustavo C et al. (2005) Reduction of Pnn by RNAi induces loss of cell-cell adhesion between human corneal epithelial cells. Mol Vis 11:133-42
Alpatov, Roman; Munguba, Gustavo Costa; Caton, Paul et al. (2004) Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene. Mol Cell Biol 24:10223-35

Showing the most recent 10 out of 20 publications