Activation of the mTOR pathway enhances PPARγ/SREBP-mediated lipid synthesis in human meibomian gland epithelial cells.

Autor: Jun I; Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea.; Department of Ophthalmology, Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, South Korea.; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Choi YJ; Department of Ophthalmology, Ajou University School of Medicine, Suwon, Republic of Korea., Kim BR; Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea.; Department of Ophthalmology, Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, South Korea., Lee HK; Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea.; Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea., Seo KY; Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea.; Department of Ophthalmology, Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, South Korea., Kim TI; Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea. tikim@yuhs.ac.; Department of Ophthalmology, Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, South Korea. tikim@yuhs.ac.; Department of Material Science and Engineering, Yonsei University, Seoul, South Korea. tikim@yuhs.ac.; Affilate Faculty, Material Research Center for Batteries, Pohang University of Science and Technology (POSTECH), Pohang, South Korea. tikim@yuhs.ac.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 15; Vol. 14 (1), pp. 28118. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1038/s41598-024-73969-6
Abstrakt: The involvement of the mechanistic targets of rapamycin (mTOR) pathway in lipid metabolism has been recently elucidated. However, its specific role in the Meibomian gland, where lipid metabolism is significant, remains not fully understood. We investigated the role of mTOR signaling system in the lipogenesis and differentiation of human meibomian gland epithelial cells (HMGECs). Treatment of HMGECs with rapamycin resulted in a reduction in lipid synthesis and the expression of PPARγ and SREBP-1, the major regulators of lipid synthesis. The phosphorylation of p70S6kinase and AKT, which are downstream signals of mTOR complexes 1 and 2, respectively, decreased following rapamycin treatment. In addition, when both mTOR complex 1 and 2 were suppressed using siRNA, there was a significant reduction in the expression of PPARγ and SREBP-1, along with a decrease in lipid synthesis in HMGECs. Our findings suggest that inhibiting the mTOR pathway diminishes the differentiation and adipogenesis of meibomian gland epithelial cells, and both mTOR complexes 1 and 2 appear to play a role in this activity.
Competing Interests: Competing interests The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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