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在肾缺血再灌注损伤和恢复猪模型中，时间和性别依赖性基因表达模式。

Temporal and sex-dependent gene expression patterns in a renal ischemia-reperfusion injury and recovery pig model.

机构信息

Renal Physiopathology Group, Vall d'Hebron Research Institute, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.

Biomedical Research in Urology Group, Vall d'Hebron Research Institute, Barcelona, Spain.

出版信息

Sci Rep. 2022 Apr 28;12(1):6926. doi: 10.1038/s41598-022-10352-3.

DOI:10.1038/s41598-022-10352-3
PMID:35484379
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9051203/
Abstract

Men are more prone to acute kidney injury (AKI) and chronic kidney disease (CKD), progressing to end-stage renal disease (ESRD) than women. Severity and capacity to regenerate after AKI are important determinants of CKD progression, and of patient morbidity and mortality in the hospital setting. To determine sex differences during injury and recovery we have generated a female and male renal ischemia/reperfusion injury (IRI) pig model, which represents a major cause of AKI. Although no differences were found in blood urea nitrogen (BUN) and serum creatinine (SCr) levels between both sexes, females exhibited higher mononuclear infiltrates at basal and recovery, while males showed more tubular damage at injury. Global transcriptomic analyses of kidney biopsies from our IRI pig model revealed a sexual dimorphism in the temporal regulation of genes and pathways relevant for kidney injury and repair, which was also detected in human samples. Enrichment analysis of gene sets revealed five temporal and four sexual patterns governing renal IRI and recovery. Overall, this study constitutes an extensive characterization of the time and sex differences occurring during renal IRI and recovery at gene expression level and offers a template of translational value for further study of sexual dimorphism in kidney diseases.

摘要

男性比女性更容易发生急性肾损伤（AKI）和慢性肾脏病（CKD），进而发展为终末期肾病（ESRD）。AKI 的严重程度和再生能力是 CKD 进展、以及患者在医院环境中发病率和死亡率的重要决定因素。为了确定损伤和恢复过程中的性别差异，我们建立了雌性和雄性肾缺血/再灌注损伤（IRI）猪模型，这是 AKI 的主要原因之一。尽管在血液尿素氮（BUN）和血清肌酐（SCr）水平方面，两性之间没有差异，但在基础和恢复时，女性表现出更高的单核细胞浸润，而男性在损伤时则表现出更多的肾小管损伤。我们对 IRI 猪模型的肾脏活检进行的全基因组转录组分析显示，与肾脏损伤和修复相关的基因和途径的时间调控存在性别二态性，这在人类样本中也有发现。基因集的富集分析揭示了五个时间和四个性别模式，可用于控制肾 IRI 和恢复。总的来说，这项研究在基因表达水平上对肾 IRI 和恢复过程中的时间和性别差异进行了广泛的描述，并为进一步研究肾脏疾病中的性别二态性提供了具有转化价值的模板。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/9051203/e6dd40cc82c6/41598_2022_10352_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/9051203/603365d83154/41598_2022_10352_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/9051203/e6dd40cc82c6/41598_2022_10352_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/9051203/df373113aea5/41598_2022_10352_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/9051203/145ac0222f4f/41598_2022_10352_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/9051203/cb352a898655/41598_2022_10352_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/9051203/98fa1178455d/41598_2022_10352_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/9051203/c9dc3bf7b8c6/41598_2022_10352_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/9051203/603365d83154/41598_2022_10352_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c0/9051203/e6dd40cc82c6/41598_2022_10352_Fig8_HTML.jpg

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