ArticleInvestigative ophthalmology & visual science2013
Role of SH2-containing tyrosine phosphatase Shp2 in mouse corneal epithelial stratification.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Glucocorticoid Receptor Signaling Is Critical for Mouse Corneal Development, Inhibition of Inflammatory Response, and Neovascularization of the Cornea.The American journal of pathology · 2024Article
- Spatiotemporally Controlled Ablation of Klf5 Results in Dysregulated Epithelial Homeostasis in Adult Mouse Corneas.Investigative ophthalmology & visual science · 2017Article
- Fibroblast Growth Factor Receptor 2 (FGFR2) Is Required for Meibomian Gland Homeostasis in the Adult Mouse.Investigative ophthalmology & visual science · 2017Article
- Wakayama symposium: role of canonical Notch signaling in conjucntival goblet cell differentiation and dry eye syndrome.BMC ophthalmology · 2015Article
- Wnt/β-catenin signaling modulates corneal epithelium stratification via inhibition of Bmp4 during mouse development.Development (Cambridge, England) · 2015Article
- Eyelid closure in embryogenesis is required for ocular adnexa development.Investigative ophthalmology & visual science · 2014Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeShp2 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.
methodsShp2 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.
resultsShp2(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/β-catenin junction and laminin-β1 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.
conclusionsThese 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.
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