Meibomian gland dysfunction is one of the main causes of dry eye disease and has limited therapeutic options. In this study, we investigated the biological function of the beta 2-adrenergic receptor (ADRB2)/protein kinase A (PKA) pathway in lipid synthesis and its underlying mechanisms in human meibomian gland epithelial cells (HMGECs). HMGECs were cultured in differentiation media with or without forskolin (an activator of adenylate cyclase), salbutamol (an ADRB2 agonist), or timolol (an ADRB2 antagonist) for up to 4 days. The phosphorylation of the cAMP-response element-binding protein (CREB) and the expression of peroxisome proliferator activator receptor (PPAR)γ and sterol regulatory element-binding protein (SREBP)-1 were measured by immunoblotting and quantitative PCR. Lipid synthesis was examined by LipidTOX immunostaining, AdipoRed assay, and Oil Red O staining. PKA pathway activation enhanced PPARγ expression and lipid synthesis in differentiated HMGECs. When treated with agonists of ADBR2 (upstream of the PKA signaling system), PPARγ expression and lipid synthesis were enhanced in HMGECs. The ADRB2 antagonist timolol showed the opposite effect. The activation of the ADRB2/PKA signaling pathway enhances lipid synthesis in HMGECs. These results provide a potential mechanism and therapeutic target for meibomian gland dysfunction, particularly in cases induced by beta-blocker glaucoma drugs.
|Journal||International journal of molecular sciences|
|Publication status||Published - 2022 Aug|
Bibliographical noteFunding Information:
This work was supported by a faculty research grant of Yonsei University College of Medicine [grant number 6-2020-0222], a new faculty research seed money grant of Yonsei University College of Medicine for 2022 [grant number 2022-32-0071], the Basic Science Research Program (NRF-2021R1I1A1A01047951) of the National Research Foundation (NRF), and by the Korean Fund for Regenerative Medicine (KFRM) grant (KFRM 22C0615L1) funded by the Korean Government (the Ministry of Science and ICT, the Ministry of Health & Welfare). The funding organization had no role in the design or conduct of this study.
© 2022 by the authors.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry