Eicosapentaenoic acid (EPA) activates PPARγ signaling leading to cell cycle exit, lipid accumulation, and autophagy in human meibomian gland epithelial cells (hMGEC)

Kim, Sun Woong; Rho, Chang Rae; Kim, Jinseor; Xie, Yong; Prince, Richard C.; Mustafa, Khawla; Potma, Eric O.; Brown, Donald J.; Jester, James V.

doi:10.1016/j.jtos.2020.04.012

Cited by 28 publications

(14 citation statements)

References 62 publications

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“…These findings indicate that PPARγ is expressed by lipid synthesizing cells (meibocytes) in mature Meibomian glands, but not in ductal epithelial cells [20,67]. Thus, PPARγ could be used as a potential marker for meibocyte differentiation [7,61,68]. As mentioned above, in humans, Meibomian gland dropout has been tightly correlated with patient age and has also been correlated with nuclear PPARγ staining [9].…”

Section: Role Of Pparγ In Mgd and Armgdmentioning

confidence: 83%

Meibomian Gland Dysfunction: What Have Animal Models Taught Us?

Sun

Moreno

Dang

et al. 2020

IJMS

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Studies have estimated that currently 344 million people worldwide and 16.4 million adults in the US have some form of dry eye disease (DED). It is believed that approximately 70% of DED cases are due to some form of evaporative dry eye, for which Meibomian gland dysfunction (MGD) is the major cause. Unfortunately, currently there is no effective treatment for MGD, and solely palliative care is available. Given the importance of MGD in DED, there has been a growing interest in studying Meibomian gland development, homeostasis and pathology, and, also, in developing therapies for treating and/or preventing MGD. For such, animal models have shown to be a vital tool. Much of what is known today about the Meibomian gland and MGD was learnt from these important animal models. In particular, canine and rabbit models have been essential for studying the physiopathology and progression of DED, and the mouse model, which includes different knockout strains, has enabled the identification of specific pathways potentially involved in MGD. Herein, we provide a bibliographic review on the various animal models that have been used to study Meibomian gland development, Meibomian gland homeostasis and MGD, primarily focusing on publications between 2000 and 2020.

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Section: Role Of Pparγ In Mgd and Armgdmentioning

confidence: 83%

Meibomian Gland Dysfunction: What Have Animal Models Taught Us?

Sun

Moreno

Dang

et al. 2020

IJMS

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“…Consistent with our findings, Guo et al 10 recently reported that there was a prominent proinflammatory cytokine response, lipid accumulation, glandular dropout, and cell death in rats with MGD induced by hyperglycemia. Kim et al 54 also suggested that autophagy was initiated and mediated for cellular disintegration during the late differentiation of HMGECs. MLT supplementation could regulate the differentiation of several cell types by mediating apoptosis and autophagy.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Attenuates LPS-Induced Proinflammatory Cytokine Response and Lipogenesis in Human Meibomian Gland Epithelial Cells via MAPK/NF-κB Pathway

Liu

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Inflammation contributes to the development of meibomian gland dysfunction (MGD) under specific disease conditions, but the underlying mechanisms remain elusive. We examined whether lipopolysaccharide (LPS) induced a proinflammatory cytokine response and lipogenesis in human meibomian gland epithelial cells (HMGECs) and whether melatonin (MLT), a powerful anti-inflammatory regent in the eyes, could protect against LPS-induced disorders. Methods Human meibomian gland (MG) tissues and immortalized HMGECs were stained to identify Toll-like receptor (TLR) 4 and MLT receptors (MT 1 and MT 2 ). HMGECs were pretreated with or without MLT and then stimulated with LPS. Then, TLR4 activation, cytokine levels, lipid synthesis, apoptosis, autophagy, and MAPK/NF-κB factor phosphorylation in HMGECs were analyzed. Results TLR4, MT 1 , and MT 2 were expressed in human MG acini and HMGECs. Pretreatment with MLT inhibited the TLR4/MyD88 signaling and attenuated proinflammatory cytokine response and lipogenesis in LPS-stimulated HMGECs, which manifested as decreased production of cytokines (IL-1β, IL-6, IL-8, and TNF-α), reduced lipid droplet formation, and downregulated expression of meibum lipogenic proteins (ADFP, ELOVL4, and SREBP-1). Phospho-histone H2A.X foci, lysosome accumulation, and cytoplasmic cleaved caspase 3/LC3B-II staining were increased in LPS-stimulated HMGECs, indicating enhanced cell death mediated by apoptosis and autophagy during LPS-induced lipogenesis. MLT downregulated cleaved caspase 3 levels and the Bax/Bcl-2 ratio to alleviate apoptosis and ameliorated the expression of Beclin 1 and LC3B-II to inhibit autophagy. The protective mechanisms of MLT include the inhibition of MAPK and NF-κB phosphorylation. Conclusions MLT attenuated lipogenesis, apoptosis, and autophagy in HMGECs induced by proinflammatory stimuli, indicating the protective potential of MLT in MGD.

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“…S 14f of the Supplementary Information ). There have been some methods to induce the formation and accumulation of lipid droplets in other cell types (non-adipocytes), such as myocardial cells 45 , monocytes 46 , astrocytes 47 , and epithelial cells 48 . The accumulation of lipid droplets in these non-adipocytes was mainly induced in biochemical ways.…”

Section: Discussionmentioning

confidence: 99%

Lipid droplets as endogenous intracellular microlenses

Chen

Gong

et al. 2021

Light Sci Appl

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Using a single biological element as a photonic component with well-defined features has become a new intriguing paradigm in biophotonics. Here we show that endogenous lipid droplets in the mature adipose cells can behave as fully biocompatible microlenses to strengthen the ability of microscopic imaging as well as detecting intra- and extracellular signals. By the assistance of biolenses made of the lipid droplets, enhanced fluorescence imaging of cytoskeleton, lysosomes, and adenoviruses has been achieved. At the same time, we demonstrated that the required excitation power can be reduced by up to 73%. The lipidic microlenses are finely manipulated by optical tweezers in order to address targets and perform their real-time imaging inside the cells. An efficient detecting of fluorescence signal of cancer cells in extracellular fluid was accomplished due to the focusing effect of incident light by the lipid droplets. The lipid droplets acting as endogenous intracellular microlenses open the intriguing route for a multifunctional biocompatible optics tool for biosensing, endoscopic imaging, and single-cell diagnosis.

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Eicosapentaenoic acid (EPA) activates PPARγ signaling leading to cell cycle exit, lipid accumulation, and autophagy in human meibomian gland epithelial cells (hMGEC)

Cited by 28 publications

References 62 publications

Meibomian Gland Dysfunction: What Have Animal Models Taught Us?

Meibomian Gland Dysfunction: What Have Animal Models Taught Us?

Melatonin Attenuates LPS-Induced Proinflammatory Cytokine Response and Lipogenesis in Human Meibomian Gland Epithelial Cells via MAPK/NF-κB Pathway

Lipid droplets as endogenous intracellular microlenses

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