NDLI: Role of SH2-Containing Tyrosine Phosphatase Shp2 in Mouse Corneal Epithelial Stratification

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Role of SH2-Containing Tyrosine Phosphatase Shp2 in Mouse Corneal Epithelial Stratification

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Role of SH2-Containing Tyrosine Phosphatase Shp2 in Mouse Corneal Epithelial Stratification

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ng, Gracia Y. Kao, Winston W. Y. Yeh, Lung-Kun Zhang, Yujin Liu, Hongshan Liu, Chia-Yang Feng, Gen-Sheng
Description	Author Affiliation: Ng GY ( Edith J. Crawley Vision Research Center/Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, Ohio.)
Abstract	PURPOSE: Shp2 protein tyrosine phosphatase mediates a wide variety of receptor tyrosine kinases (RTK) cell signaling. Herein, we investigate the role of Shp2 in corneal morphogenesis and homeostasis. METHODS: Shp2 was conditionally knocked out (Shp2(cko)) in Krt14-rtTA;tet-O-Cre;Shp2(f/f) triple transgenic mice administrated with doxycycline (Dox) from postnatal day 1 (P1) to P10, P15, and P25, respectively. In addition, corneal epithelial debridement was performed in adult (P42) mice treated with or without Dox for 8 days (from P42-P50). Mouse eyes were then subjected to histology and immunohistochemistry. RESULTS: Shp2(cko) revealed impaired stratification of conjunctival and corneal epithelia during morphogenesis. Likewise, Shp2(cko) failed to restore epithelial stratification after a corneal epithelial wound in adult Shp2(cko). At the cellular level, the ratio of proliferating cell nuclear antigen (PCNA-positive)/total basal cells remained unchanged, but cells in G2/M (survivin-positive) phase was significantly increased in Shp2(cko) as compared with those in the control littermate. Interestingly, deltaN-p63 (ΔNp63) expression and the asymmetric division of the basal cells were coincidentally dampened in Shp2(cko). Transmission electron microscopic study showed that desmosome and hemidesmosome densities were reduced in the corneal epithelium of Shp2(cko). Immunohistochemistry also demonstrated that expression of E-cadherin/ß-catenin junction and laminin-ß1 was extensively downregulated in Shp2(cko). On the other hand, corneal epithelium lacking Shp2 remained positive for K14, Pax-6, and keratin 12 (K12), suggesting that Shp2 was dispensable for the corneal epithelial-type differentiation. CONCLUSIONS: These data argued that Shp2 deficiency predominantly impacted p63-dependent cell division and cell adhesive ability, which resulted in the impairment of stratification during corneal epithelial development and wound healing.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.13-12646
Journal	Investigative Opthalmology & Visual Science
Issue Number	13
Volume Number	54
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2013-12-03
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Carrier Proteins Physiology Epithelium, Corneal Metabolism Animals Cell Count Cell Differentiation Cornea Ultrastructure Corneal Injuries Disease Models, Animal Growth & Development Immunohistochemistry Mice Mice, Transgenic Microscopy, Electron, Transmission Morphogenesis Signal Transduction Src Homology Domains Comparative Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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