PPARγ regulates meibocyte differentiation and lipid synthesis of cultured human meibomian gland epithelial cells (hMGEC).
PPARγ regulates meibocyte differentiation and lipid synthesis of cultured human meibomian gland epithelial cells (hMGEC).
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DOI：
10.1016/j.jtos.2018.07.004
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Jester JV
中科院分区：
文献类型：
--
作者：
Kim SW;Xie Y;Nguyen PQ;Bui VT;Huynh K;Kang JS;Brown DJ;Jester JV
评估 PPARγ 在调节人睑板腺上皮细胞系 (hMGEC) 睑板细胞分化和脂质合成中的作用。 HMGEC 暴露于 10-50 μM 的 PPARγ 激动剂罗格列酮。培养物还暴露于特定的 PPARγ 拮抗剂 T0070907，以阻断 PPARγ 受体信号传导。然后用 Ki-67 和 LipidTox 对细胞进行染色，以确定分别对细胞周期和脂质合成的影响。通过定量 PCR 和蛋白质印迹评估睑板细胞分化相关蛋白 ADFP、PPARγ、ELOVL4 和 FABP4 的表达。人角膜上皮细胞系（hTCEpi）用作对照。罗格列酮在 2 天内以剂量依赖性方式显着降低 Ki-67 染色（P = 0.003），并以剂量依赖性方式增加 hMGEC 中的脂质积累。 T0070907 抑制脂滴合成和细胞周期退出。罗格列酮使 hMGEC 中 ADFP、PPARγ、ELOVL4 和 FABP4 的表达显着上调，平均上调 9.6、2.7、2.6 和 3.3 倍（除 FABP4 外，所有 P < 0.05，P = 0.057）。在罗格列酮治疗之前进行治疗时，T0070907 显着消除了罗格列酮诱导的这些基因的上调（所有 P < 0.05）。暴露于罗格列酮后，hTCEpi 中观察到的脂肪生成分化反应并未重复。罗格列酮诱导细胞周期退出和脂肪生成基因表达上调，导致 hMGEC 中脂质积累。这些效应被 PPARγ 拮抗剂抑制，表明 PPARγ 信号传导特异性指导 hMGEC 中的脂肪生成。这些发现表明 PPARγ 在睑板细胞分化中发挥着关键作用。
To evaluate the role of PPARγ in regulating meibocyte differentiation and lipid synthesis in a human meibomian gland epithelial cell line (hMGEC). HMGEC were exposed to the PPARγ agonist, Rosiglitazone, from 10–50 μM. Cultures were also exposed to specific PPARγ antagonist, T0070907, to block PPARγ receptor signaling. Cells were then stained with Ki-67 and LipidTox to determine the effects on cell cycling and lipid synthesis, respectively. Expression of meibocyte differentiation related proteins, ADFP, PPARγ, ELOVL4, and FABP4, were evaluated by quantitative PCR and western blotting. A human corneal epithelial cell line (hTCEpi) was used as a control. Rosiglitazone significantly decreased Ki-67 staining within 2 days in a dose-dependent manner (P = 0.003) and increased lipid accumulation in hMGEC in a dose dependent manner. T0070907 suppressed both lipid droplet synthesis and cell cycle exit. Rosiglitazone significantly upregulated expression of ADFP, PPARγ, ELOVL4, and FABP4 by 9.6, 2.7, 2.6, and 3.3 fold on average (all P < 0.05 except for FABP4, P = 0.057) in hMGEC. T0070907 significantly abrogated rosiglitazone-induced upregulation of these genes when treated prior to rosiglitazone treatment (all P < 0.05). The observed lipogenic differentiation response was not duplicated in hTCEpi after exposure to rosiglitazone. Rosiglitazone induced cell cycle exit and upregulation of lipogenic gene expression leading to lipid accumulation in hMGEC. These effects were suppressed by PPARγ antagonist indicating that PPARγ signaling specifically directs lipogenesis in hMGEC. These findings suggest that PPARγ plays a critical role in meibocyte differentiation.
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DOI：
10.1016/j.jtos.2017.03.006
发表时间：
2017-07
期刊：
The ocular surface
影响因子：
--
作者：
Willcox MDP;Argüeso P;Georgiev GA;Holopainen JM;Laurie GW;Millar TJ;Papas EB;Rolland JP;Schmidt TA;Stahl U;Suarez T;Subbaraman LN;Uçakhan OÖ;Jones L
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Jones L
DOI：
10.4137/cmc.s17067
发表时间：
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期刊：
Clinical Medicine Insights. Cardiology
影响因子：
--
作者：
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通讯作者：
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影响因子：
--
作者：
Nien, Chyong Jy;Massei, Salina;Lin, Gloria;Nabavi, Cameron;Tao, Jeremiah;Brown, Donald J.;Paugh, Jerry R.;Jester, James V.
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Jester, James V.
影响因子：
3.4
作者：
Schroeder, Antje;Abrar, Daniel B.;Garreis, Fabian
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影响因子：
3.4
作者：
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通讯作者：
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