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Periplocin ameliorates mouse age-related meibomian gland dysfunction through up-regulation of Na/K-ATPase via SRC
Huifeng Wang1, Zongzheng Zou2, Luqin Wan1
1Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University Qingdao, China.
Abstract:
Age-related meibomian gland dysfunction (MGD) is the main cause of evaporative dry eye disease in an aging population. Decreased meibocyte cell renewal and lipid synthesis are associated with age-related MGD. Here, we found an obvious decline of Ki67, ΔNp63, and Na+/K+ ATPase expression in aged meibomian glands. Potential Na+/K+ ATPase agonist periplocin, a naturally occurring compound extracted from the traditional herbal medicine cortex periplocae, could promote the proliferation and stem cell activity of meibocyte cells in vitro. Moreover, we observed that periplocin treatment effectively increased the expression of Na+ /K+ ATPase, accompanied with the enhanced expression of Ki67 and ΔNp63 in aged meibomian glands, indicating that periplocin may accelerate meibocyte cell renewal in aged mice. LipidTox staining showed increased lipid accumulation after periplocin treatment in cultured meibomian gland cells and aged meibomian glands. Furthermore, we demonstrated that the SRC pathway was inhibited in aged meibomian glands; however, it was activated by periplocin. Accordingly, the inhibition of the SRC signaling pathway by saracatinib blocked periplocin-induced proliferation and lipid accumulation in meibomian gland cells. In sum, we suggest periplocin-ameliorated meibocyte cell renewal and lipid synthesis in aged meibomian glands via the SRC pathway, which could be a promising candidate for age-related MGD.
Insights
Periplocin, a natural compound, rejuvenates aged meibomian glands by boosting meibocyte renewal and lipid production. This treatment targets the SRC pathway, offering a potential therapy for age-related evaporative dry eye disease.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Age-related meibomian gland dysfunction (MGD) is a primary cause of evaporative dry eye.
- Reduced meibocyte renewal and lipid synthesis contribute to MGD in aging individuals.
- Key markers like Ki67, ΔNp63, and Na+/K+ ATPase decline in aged meibomian glands.
Purpose of the Study:
- To investigate the potential of periplocin, a Na+/K+ ATPase agonist, in treating age-related MGD.
- To elucidate the mechanism of periplocin's action on meibocyte renewal and lipid synthesis.
- To explore the role of the SRC pathway in periplocin's therapeutic effects.
Main Methods:
- In vitro studies on meibocyte cell proliferation and stem cell activity.
- In vivo studies using aged mice models.
- Analysis of protein expression (Ki67, ΔNp63, Na+/K+ ATPase, SRC pathway markers).
- Lipid accumulation assessment using LipidTox staining.
- Pharmacological inhibition of the SRC pathway using saracatinib.
Main Results:
- Periplocin promoted meibocyte proliferation and stem cell activity in vitro.
- In aged mice, periplocin increased Na+/K+ ATPase, Ki67, and ΔNp63 expression, enhancing meibocyte renewal.
- Periplocin treatment led to increased lipid accumulation in meibomian gland cells and tissues.
- Aged meibomian glands showed inhibited SRC pathway activity, which periplocin reversed.
- Inhibiting the SRC pathway blocked periplocin's positive effects on proliferation and lipid synthesis.
Conclusions:
- Periplocin enhances meibocyte cell renewal and lipid synthesis in aged meibomian glands.
- The therapeutic effects of periplocin are mediated through the SRC signaling pathway.
- Periplocin shows promise as a therapeutic agent for age-related MGD.
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