97 242

Cited 4 times in

Activation of ADRB2/PKA Signaling Pathway Facilitates Lipid Synthesis in Meibocytes, and Beta-Blocker Glaucoma Drug Impedes PKA-Induced Lipid Synthesis by Inhibiting ADRB2

Authors
 Ikhyun Jun  ;  Young Joon Choi  ;  Bo-Rahm Kim  ;  Kyoung Yul Seo  ;  Tae-Im Kim 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.23(16) : 9478, 2022-08 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2022-08
MeSH
Adrenergic beta-Antagonists* / pharmacology ; Cyclic AMP-Dependent Protein Kinases* / metabolism ; Glaucoma* / drug therapy ; Humans ; Lipids / biosynthesis ; Meibomian Gland Dysfunction* ; PPAR gamma / metabolism ; Receptors, Adrenergic, beta-2* / metabolism ; Signal Transduction ; Timolol / pharmacology
Keywords
ADRB2 ; PPARγ ; lipogenesis ; meibomian gland dysfunction ; protein kinase A ; timolol
Abstract
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.
Files in This Item:
T202203495.pdf Download
DOI
10.3390/ijms23169478
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Bo Ram(김보람)
Kim, Tae-Im(김태임) ORCID logo https://orcid.org/0000-0001-6414-3842
Seo, Kyoung Yul(서경률) ORCID logo https://orcid.org/0000-0002-9855-1980
Jun, Ik Hyun(전익현) ORCID logo https://orcid.org/0000-0002-2160-1679
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191835
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links