1. Academic Validation
  2. Periplocin ameliorates mouse age-related meibomian gland dysfunction through up-regulation of Na/K-ATPase via SRC pathway

Periplocin ameliorates mouse age-related meibomian gland dysfunction through up-regulation of Na/K-ATPase via SRC pathway

  • Biomed Pharmacother. 2022 Feb;146:112487. doi: 10.1016/j.biopha.2021.112487.
Huifeng Wang 1 Zongzheng Zou 2 Luqin Wan 1 Junfa Xue 2 Chen Chen 2 Bingjie Yu 2 Zhenzhen Zhang 2 Lingling Yang 3 Lixin Xie 4
Affiliations

Affiliations

  • 1 Qingdao 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.
  • 2 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University Qingdao, China.
  • 3 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University Qingdao, China. Electronic address: [email protected].
  • 4 Qingdao 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. Electronic address: [email protected].
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.

Keywords

Aging; Cell proliferation; Lipid accumulation; Meibomian gland dysfunction; Na+/K+-ATPase; Periplocin.

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