IUGR decreases PPARγ and SETD8 Expression in neonatal rat lung and these effects are ameliorated by maternal DHA supplementation.
IUGR decreases PPARγ and SETD8 Expression in neonatal rat lung and these effects are ameliorated by maternal DHA supplementation.
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DOI：
10.1016/j.earlhumdev.2010.08.026
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发表时间：
2010-12
影响因子：
2.5
通讯作者：
Lane, Robert H.
中科院分区：
文献类型：
--
作者：
Joss-Moore, Lisa A.;Wang, Yan;Baack, Michelle L.;Yao, Jianrong;Norris, Andrew W.;Yu, Xing;Callaway, Christopher W.;McKnight, Robert A.;Albertine, Kurt H.;Lane, Robert H.
宫内生长限制（IUGR）与人类和大鼠肺发育改变有关。转录因子PPARγ被认为有助于肺部发育。PPARγ被二十二碳己酸（DHA）激活。PPARγ对肺发育的一个贡献可能是它直接调节染色质修饰酶，如Setd8。在这项研究中，我们假设IUGR会导致新生儿大鼠肺中PPARγ、Setd8和相关H4K20Me水平的性别特异性降低。由于DHA激活了PPARγ，我们也假设母体补充DHA会使IUGR大鼠肺中PPARγ、Setd8和H4K20Me水平正常化。我们发现IUGR降低了雄性和雌性大鼠肺中的PPARγ水平，并伴有Setd8水平的相关降低。在男性和女性的PPARγ基因上，setd8依赖性组蛋白修饰H4K20Me的水平均降低，而全肺H4K20Me仅在男性肺中降低。母体补充DHA可以改善后代的这些影响。我们得出结论，IUGR降低肺PPARγ、Setd8和PPARγ H4K20Me与性别无关，而仅在男性中降低全肺H4K20Me。这些结果被母体DHA所抵消。我们推测，表观遗传环境的维持可能是PPARγ在肺中的一个作用，并提示母体DHA补充在IUGR中的新益处。
Intrauterine growth restriction (IUGR) is associated with altered lung development in human and rat. The transcription factor PPARγ, is thought to contribute to lung development. PPARγ is activated by docosahexanoic acid (DHA). One contribution of PPARγ to lung development may be its direct regulation of chromatin modifying enzymes, such as Setd8. In this study, we hypothesized that IUGR would result in a gender-specific reduction in PPARγ, Setd8 and associated H4K20Me levels in the neonatal rat lung. Because DHA activates PPARγ, we also hypothesized that maternal DHA supplementation would normalize PPARγ, Setd8, and H4K20Me levels in the IUGR rat lung. We found that IUGR decreased PPARγ levels, with an associated decrease in Setd8 levels in both male and female rat lungs. Levels of the Setd8-dependent histone modification, H4K20Me, were reduced on the PPARγ gene in both males and females while whole lung H4K20Me was only reduced in male lung. Maternal DHA supplementation ameliorated these effects in offspring. We conclude that IUGR decreases lung PPARγ, Setd8 and PPARγ H4K20Me independent of gender, while decreasing whole lung H4K20Me in males only. These outcomes are offset by maternal DHA. We speculate that maintenance of the epigenetic milieu may be one role of PPARγ in the lung and suggest a novel benefit of maternal DHA supplementation in IUGR.
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影响因子：
3.7
作者：
Aoki, Yasuhiro;Maeno, Toshitaka;Kurabayashi, Masahiko
通讯作者：
Kurabayashi, Masahiko
DOI：
10.1016/j.bbrc.2008.05.155
发表时间：
2008-08-08
影响因子：
3.1
作者：
Guillot, Nicolas;Debard, Cyrille;Vericel, Evelyne
通讯作者：
Vericel, Evelyne
DOI：
10.1164/ajrccm.164.10.2101140
发表时间：
2001-11-15
影响因子：
24.7
作者：
Bhatt, AJ;Pryhuber, GS;Maniscalco, WM
通讯作者：
Maniscalco, WM
影响因子：
2.8
作者：
Coyne, G. S.;Kenny, D. A.;Waters, S. M.
通讯作者：
Waters, S. M.
影响因子：
2.5
作者：
Joss-Moore, Lisa A.;Wang, Yan;Campbell, Michael S.;Moore, Barry;Yu, Xing;Callaway, Christopher W.;McKnight, Robert A.;Desai, Mina;Moyer-Mileur, Laurie J.;Lane, Robert H.
通讯作者：
Lane, Robert H.