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Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat.

Xu XF, Hu QY, Liang LF, Wu L, Gu WZ, Tang LL, Fu LC, Du LZ - Respir. Res. (2014)

Bottom Line: The effect was maintained until 10 weeks after birth.Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China. xuxuefeng@zju.edu.cn.

ABSTRACT

Background: Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.

Methods: An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR.

Results: Maternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.

Conclusions: These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.

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Related in: MedlinePlus

Comparison of histone H3 (A), H3K9 (B), and H4 (C) acetylation levels at theET-1promoter between IUGR and control rats using ChIP and relative quantitative real-time PCR. A1 and A2 represent two areas of the ET-1 gene promoter (−197 to +25, and −397 to −179, respectively). Data are expressed as IUGR percent of the Control ± SEM. *P <0.05 as compared with Control groups. Note that the levels of acetylated histone H3 and H3K9 in the ET-1 promoter A1 region of lung tissue from IUGR groups were significantly higher than those from the age-matched Control groups; while in the ET-1 promoter A2 region there was no significant statistical difference between IUGR and Control groups. The level of acetylated histone H4 in the ET-1 promoter A1 region of the IUGR OVA group was significantly higher than that of the Control OVA group (n = 4).
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Fig6: Comparison of histone H3 (A), H3K9 (B), and H4 (C) acetylation levels at theET-1promoter between IUGR and control rats using ChIP and relative quantitative real-time PCR. A1 and A2 represent two areas of the ET-1 gene promoter (−197 to +25, and −397 to −179, respectively). Data are expressed as IUGR percent of the Control ± SEM. *P <0.05 as compared with Control groups. Note that the levels of acetylated histone H3 and H3K9 in the ET-1 promoter A1 region of lung tissue from IUGR groups were significantly higher than those from the age-matched Control groups; while in the ET-1 promoter A2 region there was no significant statistical difference between IUGR and Control groups. The level of acetylated histone H4 in the ET-1 promoter A1 region of the IUGR OVA group was significantly higher than that of the Control OVA group (n = 4).

Mentions: Two sites in the ET-1 gene promoter were analyzed for acetylated histone H3, H3K9, and H4. Acetylation levels of each site in the IUGR groups were quantified by ChIP/real-time PCR and are expressed as a fold-change relative to the same site in the age-matched Control groups. The levels of acetylated histone H3 in the ET-1 promoter A1 region of lung tissue from IUGR d1, IUGR 10wks, and IUGR OVA groups were significantly higher than those from the age-matched Control groups (P = 0.039, 0.025, and 0.008, respectively). In the ET-1 promoter A2 region, there was no statistically significant difference between IUGR and Control groups (P >0.05, Figure 6A). A trend of acetylated H3K9 levels in the ET-1 promoter in lung tissue was similar to the observed change in acetylated histone H3 (Figure 6B).Figure 6


Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat.

Xu XF, Hu QY, Liang LF, Wu L, Gu WZ, Tang LL, Fu LC, Du LZ - Respir. Res. (2014)

Comparison of histone H3 (A), H3K9 (B), and H4 (C) acetylation levels at theET-1promoter between IUGR and control rats using ChIP and relative quantitative real-time PCR. A1 and A2 represent two areas of the ET-1 gene promoter (−197 to +25, and −397 to −179, respectively). Data are expressed as IUGR percent of the Control ± SEM. *P <0.05 as compared with Control groups. Note that the levels of acetylated histone H3 and H3K9 in the ET-1 promoter A1 region of lung tissue from IUGR groups were significantly higher than those from the age-matched Control groups; while in the ET-1 promoter A2 region there was no significant statistical difference between IUGR and Control groups. The level of acetylated histone H4 in the ET-1 promoter A1 region of the IUGR OVA group was significantly higher than that of the Control OVA group (n = 4).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4233040&req=5

Fig6: Comparison of histone H3 (A), H3K9 (B), and H4 (C) acetylation levels at theET-1promoter between IUGR and control rats using ChIP and relative quantitative real-time PCR. A1 and A2 represent two areas of the ET-1 gene promoter (−197 to +25, and −397 to −179, respectively). Data are expressed as IUGR percent of the Control ± SEM. *P <0.05 as compared with Control groups. Note that the levels of acetylated histone H3 and H3K9 in the ET-1 promoter A1 region of lung tissue from IUGR groups were significantly higher than those from the age-matched Control groups; while in the ET-1 promoter A2 region there was no significant statistical difference between IUGR and Control groups. The level of acetylated histone H4 in the ET-1 promoter A1 region of the IUGR OVA group was significantly higher than that of the Control OVA group (n = 4).
Mentions: Two sites in the ET-1 gene promoter were analyzed for acetylated histone H3, H3K9, and H4. Acetylation levels of each site in the IUGR groups were quantified by ChIP/real-time PCR and are expressed as a fold-change relative to the same site in the age-matched Control groups. The levels of acetylated histone H3 in the ET-1 promoter A1 region of lung tissue from IUGR d1, IUGR 10wks, and IUGR OVA groups were significantly higher than those from the age-matched Control groups (P = 0.039, 0.025, and 0.008, respectively). In the ET-1 promoter A2 region, there was no statistically significant difference between IUGR and Control groups (P >0.05, Figure 6A). A trend of acetylated H3K9 levels in the ET-1 promoter in lung tissue was similar to the observed change in acetylated histone H3 (Figure 6B).Figure 6

Bottom Line: The effect was maintained until 10 weeks after birth.Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China. xuxuefeng@zju.edu.cn.

ABSTRACT

Background: Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.

Methods: An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR.

Results: Maternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.

Conclusions: These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.

Show MeSH
Related in: MedlinePlus