Ikhyun Jun1, Bo-Rahm Kim2, Sun Young Park2, Hun Lee3, Jiyeon Kim4, Eung Kweon Kim1, Kyoung Yul Seo4, Tae-Im Kim5. 1. The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemungu, Seoul, 03722, South Korea; Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemungu, Seoul, 03722, South Korea. 2. The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemungu, Seoul, 03722, South Korea. 3. The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemungu, Seoul, 03722, South Korea; Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea. 4. The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemungu, Seoul, 03722, South Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemungu, Seoul, 03722, South Korea. 5. The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemungu, Seoul, 03722, South Korea; Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemungu, Seoul, 03722, South Korea. Electronic address: tikim@yuhs.ac.
Abstract
PURPOSE: This study was performed to investigate the effects of interleukin (IL)-4 on adipogenesis and the underlying molecular mechanisms in human meibomian gland epithelial cells (HMGECs). METHODS: HMGECs and human white preadipocytes (HWPs) were cultured and differentiated with or without IL-4. Oil-red O staining, Adipored assay, and LipidTox immunostaining were performed to examine the extent of lipid droplet formation. The expression of signal transducer and activator of transcription 6 (STAT6), phospho-STAT6, peroxisome proliferator activator receptor (PPAR)γ, and sterol regulatory element-binding protein (SREBP)-1 was measured through immunoblotting. Cells were treated with STAT6 inhibitor, which prevents the phosphorylation of STAT6 by IL-4, to determine whether the effects of IL-4 on lipogenesis were altered. RESULTS: Treatment with IL-4 significantly facilitated lipid production in differentiated HMGECs. Phosphorylation of STAT6 and expression of key adipogenesis-related molecules PPARγ and SREBP-1 were increased after IL-4 treatment. Inhibition of STAT6 phosphorylation suppressed IL-4-mediated lipid synthesis in HMGECs. In contrast, the lipid synthetic effects of IL-4 were not observed in differentiated HWPs. CONCLUSIONS: IL-4 appears to promote lipid synthesis in meibomian gland epithelial cells through the STAT6/PPARγ signaling pathway. This mechanism can serve as a potential therapeutic target for meibomian gland dysfunction.
PURPOSE: This study was performed to investigate the effects of interleukin (IL)-4 on adipogenesis and the underlying molecular mechanisms in human meibomian gland epithelial cells (HMGECs). METHODS: HMGECs and human white preadipocytes (HWPs) were cultured and differentiated with or without IL-4. Oil-red O staining, Adipored assay, and LipidTox immunostaining were performed to examine the extent of lipid droplet formation. The expression of signal transducer and activator of transcription 6 (STAT6), phospho-STAT6, peroxisome proliferator activator receptor (PPAR)γ, and sterol regulatory element-binding protein (SREBP)-1 was measured through immunoblotting. Cells were treated with STAT6 inhibitor, which prevents the phosphorylation of STAT6 by IL-4, to determine whether the effects of IL-4 on lipogenesis were altered. RESULTS: Treatment with IL-4 significantly facilitated lipid production in differentiated HMGECs. Phosphorylation of STAT6 and expression of key adipogenesis-related molecules PPARγ and SREBP-1 were increased after IL-4 treatment. Inhibition of STAT6 phosphorylation suppressed IL-4-mediated lipid synthesis in HMGECs. In contrast, the lipid synthetic effects of IL-4 were not observed in differentiated HWPs. CONCLUSIONS:IL-4 appears to promote lipid synthesis in meibomian gland epithelial cells through the STAT6/PPARγ signaling pathway. This mechanism can serve as a potential therapeutic target for meibomian gland dysfunction.