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过氧化物酶体增殖物激活受体 γ(PPARγ)调控炎症子宫内膜中 DNA 损伤反应相关基因的表达。

PPARγ regulates the expression of genes involved in the DNA damage response in an inflamed endometrium.

机构信息

Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 1a, 10-719, Olsztyn, Poland.

Department of Plant Physiology, Genetics and Biotechnology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 1a, 10-719, Olsztyn, Poland.

出版信息

Sci Rep. 2022 Mar 7;12(1):4026. doi: 10.1038/s41598-022-07986-8.

Abstract

Inflammation is a biological response of the immune system, which can be triggered by many factors, including pathogens. These factors may induce acute or chronic inflammation in various organs, including the reproductive system, leading to tissue damage or disease. In this study, the RNA-Seq technique was used to determine the in vitro effects of peroxisome proliferator-activated receptor gamma (PPARγ) ligands on the expression of genes and long non-coding RNA, and alternative splicing events (ASEs) in LPS-induced inflammation of the porcine endometrium during the follicular phase of the estrous cycle. Endometrial slices were incubated in the presence of LPS and PPARγ agonists (PGJ or pioglitazone) and a PPARγ antagonist (T0070907). We identified 169, 200, 599 and 557 differentially expressed genes after LPS, PGJ, pioglitazone or T0070907 treatment, respectively. Moreover, changes in differentially expressed long non-coding RNA and differential alternative splicing events were described after the treatments. The study revealed that PPARγ ligands influence the LPS-triggered expression of genes controlling the DNA damage response (GADD45β, CDK1, CCNA1, CCNG1, ATM). Pioglitazone treatment exerted a considerable effect on the expression of genes regulating the DNA damage response.

摘要

炎症是免疫系统的一种生物反应,可以由许多因素触发,包括病原体。这些因素可能会导致包括生殖系统在内的各种器官发生急性或慢性炎症,导致组织损伤或疾病。在这项研究中,我们使用 RNA-Seq 技术来确定过氧化物酶体增殖物激活受体 γ (PPARγ) 配体在体外对发情周期卵泡期猪子宫内膜 LPS 诱导的炎症中基因和长非编码 RNA 的表达以及选择性剪接事件 (ASEs) 的影响。将子宫内膜切片在 LPS 和 PPARγ 激动剂 (PGJ 或吡格列酮) 和 PPARγ 拮抗剂 (T0070907) 的存在下孵育。分别用 LPS、PGJ、吡格列酮或 T0070907 处理后,我们鉴定出 169、200、599 和 557 个差异表达基因。此外,还描述了处理后差异表达长非编码 RNA 和差异选择性剪接事件的变化。研究表明,PPARγ 配体影响 LPS 触发的控制 DNA 损伤反应的基因表达 (GADD45β、CDK1、CCNA1、CCNG1、ATM)。吡格列酮处理对调节 DNA 损伤反应的基因表达有很大的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd4e/8901773/4c04c6024a23/41598_2022_7986_Fig1_HTML.jpg

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