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Hif1a 在母体或成年 BPA 暴露诱导的胰腺损伤中的重要作用。

Important roles of Hif1a in maternal or adult BPA exposure induced pancreatic injuries.

机构信息

Department of Cardiopulmonary Function Examination, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, China.

Department of Clinical Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.

出版信息

Sci Rep. 2023 Jul 17;13(1):11502. doi: 10.1038/s41598-023-38614-8.

DOI:10.1038/s41598-023-38614-8
PMID:37460698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10352259/
Abstract

Bisphenol A (BPA) is a monomer to produce polycarbonate plastics and can be released into the environment through human activities, leading to its accumulation in animals, plants and humans through direct contact or environmental exposure. Epidemiological studies have reported that BPA exposure is associated with metabolic disorders. The pancreas is an important endocrine organ and plays an important role in metabolic disorders. To explore the possible long-term effects of BPA exposure on neonatal health, bioinformatic methods were used to identify differentially expressed genes (DEGs) by comparing the neonatal pancreas after maternal exposure to BPA with the adult pancreas after direct exposure to BPA. Two datasets about BPA exposure and pancreatic abnormality, GSE82175 and GSE126297 in Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) were collected. Control (or BPA-exposed) offspring (maternal exposure) and Control (or BPA-exposed) adults (direct exposure) were defined as Control (or BPA) groups. The results showed that BPA disturbed the normal function of the pancreas in both offspring and adults, with offspring showing higher susceptibility to BPA than adults. Seventeen insulin secretion-related DEGs (Stxbp5l, Fam3d, Mia3, Igf1, Hif1a, Aqp1, Kif5b, Tiam1, Map4k4, Cyp51, Pde1c, Rab3c, Arntl, Clock, Edn3, Kcnb1, and Krt20) in the BPA group were identified, and 15 regulator DEGs (Zfp830, 4931431B13Rik, Egr1, Ddit4l, Cep55, G530011O06Rik, Hspa1b, Hspa1a, Cox6a2, Ibtk, Banf1, Slc35b2, Golt1b, Lrp8, and Pttg1) with opposite expression trends and a regulator gene Cerkl with the similar expression trend in the Control and BPA groups were identified. Hif1α might be an important molecular target for pancreatic cancer caused by BPA exposure, and pregnancy is a critical window of susceptibility to BPA exposure.

摘要

双酚 A(BPA)是生产聚碳酸酯塑料的单体,可通过人类活动释放到环境中,通过直接接触或环境暴露,在动物、植物和人类中积累。流行病学研究报告称,BPA 暴露与代谢紊乱有关。胰腺是一个重要的内分泌器官,在代谢紊乱中起着重要作用。为了探索 BPA 暴露对新生儿健康的可能长期影响,本研究通过比较母体暴露 BPA 后的新生儿胰腺和直接暴露 BPA 后的成年胰腺,使用生物信息学方法鉴定差异表达基因(DEGs)。本研究从美国国立生物技术信息中心(NCBI)的基因表达综合数据库(GEO)中收集了两个关于 BPA 暴露和胰腺异常的数据集 GSE82175 和 GSE126297。对照组(或 BPA 暴露)后代(母体暴露)和对照组(或 BPA 暴露)成年(直接暴露)被定义为对照组(或 BPA)组。结果表明,BPA 扰乱了后代和成年胰腺的正常功能,后代对 BPA 的敏感性高于成年。在 BPA 组中鉴定出 17 个与胰岛素分泌相关的 DEGs(Stxbp5l、Fam3d、Mia3、Igf1、Hif1a、Aqp1、Kif5b、Tiam1、Map4k4、Cyp51、Pde1c、Rab3c、Arntl、Clock、Edn3、Kcnb1 和 Krt20),在对照组和 BPA 组中鉴定出 15 个调控 DEGs(Zfp830、4931431B13Rik、Egr1、Ddit4l、Cep55、G530011O06Rik、Hspa1b、Hspa1a、Cox6a2、Ibtk、Banf1、Slc35b2、Golt1b、Lrp8 和 Pttg1)和一个表达趋势相似的调控基因 Cerkl。Hif1α 可能是 BPA 暴露引起胰腺癌的重要分子靶点,妊娠是对 BPA 暴露易感性的关键窗口期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/10352259/9e12d81f971e/41598_2023_38614_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/10352259/9e12d81f971e/41598_2023_38614_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/10352259/8b34039d338c/41598_2023_38614_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/10352259/04cd2e86612f/41598_2023_38614_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/10352259/5aec1556cb96/41598_2023_38614_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/10352259/860a78a66ccf/41598_2023_38614_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/10352259/4ff2eb046b9d/41598_2023_38614_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/10352259/8935a0fec030/41598_2023_38614_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/10352259/8149e45deb90/41598_2023_38614_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/10352259/9e12d81f971e/41598_2023_38614_Fig8_HTML.jpg

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