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Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
SH2 domain-containing protein tyrosine phosphatase-2 is enriched in eyelid specimens of rosacea
Apoorv Chebolu1, Ramon Bossardi Ramos2, Thilaka Arunachalam1
1Department of Ophthalmology Lions Eye Institute Albany New York USA.
Background:
Rosacea is a cutaneous disease that may secondarily affect the ocular surface. Due to the vision threatening, cosmetic, psychological, and work productivity impact, the identification of cellular targets that govern rosacea would enhance our understanding of the biology of the disease and delineate targets for therapeutic manipulation.
Objective:
To characterize the involvement of SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) in the pathogenesis of rosacea.
Methods:
Specimens from elective ectropion surgery (n = 20) were processed from patients with rosacea (n = 10) and control patients (n = 10). Immunohistochemistry (IHC) and quantitative western blotting (WB) were performed to identify and quantify the presence of SHP2 and 4G10 (a phosphotyrosine antibody) in rosacea compared to normal tissue. IHC samples were graded according to an intensity scale (0-4). Mann-Whitney statistical analyses were performed via a dedicated computerized software package.
Results:
On WB, SHP2 was expressed in higher concentrations in rosacea specimens (p < 0.05). On IHC, SHP2 was enriched in the epidermis in rosacea (p < 0.05), although 4G10 levels were not statistically significantly different between the two groups (p > 0.05).
Conclusions:
SHP2 is enriched in cutaneous specimens of rosacea, suggesting a critical role for this protein in the disease and indicating a modifiable therapeutic moiety.
Insights
SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) is significantly increased in rosacea skin. This finding suggests SHP2 plays a key role in rosacea pathogenesis and may be a therapeutic target.
Area of Science:
- Dermatology
- Molecular Biology
- Immunology
Background:
- Rosacea is a common skin condition impacting vision, appearance, and quality of life.
- Identifying cellular targets is crucial for understanding rosacea and developing treatments.
Purpose of the Study:
- To investigate the role of SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) in rosacea.
- To determine if SHP2 is a potential therapeutic target for rosacea.
Main Methods:
- Compared skin specimens from rosacea patients (n=10) and controls (n=10) using immunohistochemistry (IHC) and western blotting (WB).
- Quantified SHP2 and phosphotyrosine (4G10) levels in tissue samples.
- Statistical analysis using Mann-Whitney tests.
Main Results:
- SHP2 protein levels were significantly higher in rosacea specimens compared to controls (p < 0.05).
- SHP2 was notably enriched in the epidermis of rosacea skin.
- No significant difference in 4G10 levels was observed between groups (p > 0.05).
Conclusions:
- SHP2 is upregulated in rosacea skin, indicating its involvement in the disease.
- SHP2 represents a potential therapeutic target for managing rosacea.
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