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Chia-Yang Liu, Lingling Zhang, Yuka Okada, Yen-Chiao Wang, Yujin Zhang; Shp2 regulates the expression of ΔNp63-alpha in corneal basal epithelial cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1377. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
ΔNp63-alpha plays critical roles in corneal epithelial stratification during development in the mouse. Our previous data showed that Shp2 may regulate the expression of ΔNp63-alpha in mouse corneal epithelial basal cells. In this study, experiments were performed to investigate the possible mechanism in vivo and in vitro.
Compound transgenic mouse strains in which Shp2 was conditionally ablated (Shp2cKO) or a gain-of-function mutant Shp2 was overexpressed (Shp2cGOF) in mouse corneal epithelial basal cells were generated. The human SHP2 cDNA or siRNA against SHP2 was transfected into telomerase immortalized human corneal epithelial cells (HTCE) to manipulate the expression of SHP2. The changes in mRNAs and proteins of Shp2 and ΔNp63-alpha were detected in vivo and in vitro by immunohistochemistry and western blot analysis.
The corneal epithelium stratification was impaired in Shp2cKO in which ΔNp63-alpha expressions at mRNA and protein level were dramatically reduced in corneal basal epithelial cells. Likewise, ΔNp63-alpha expression level was declined in HTCE transfected with siRNA against SHP2. Interestingly, however, two to three layers of basal columnar cells which are ΔNp63-alpha positive were observed in the corneal epithelium of the adult Shp2cGOF mice. Overexpressing of Shp2cGOF restore corneal stratification impairment observed in the Shp2cKO. Surprisingly, however, overexpression of SHP2 also downregulated ΔNp63-alpha level resulted from the rapid degradation of ΔNp63-alpha through ubiquitination pathway in HTCE cells.
Taken together, these data argued that SHP2 dosage play a pivotal role of controlling ΔNp63-alpha in corneal basal epithelial cells which in turn regulate corneal epithelium stratification.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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