研究动态
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年老大鼠肾脏中TNF信号和ECM相关基因表达的性别差异。

Sex-Mediated Differences in TNF Signaling- and ECM-Related Gene Expression in Aged Rat Kidney.

发表日期:2023
作者: Sang Gyun Noh, Hee Jin Jung, Seungwoo Kim, Radha Arulkumar, Ki Wung Chung, Daeui Park, Yeon Ja Choi, Hae Young Chung
来源: GENES & DEVELOPMENT

摘要:

衰老导致生物体功能下降,这与年龄和性别有关。为了了解肾脏功能变化的年龄和性别依赖性,我们使用从大鼠肾脏中的RNA测序(RNA-Seq)数据进行转录组分析。根据年龄和性别生成了四个不同表达的基因(DEG)组,对DEG组进行了基因本体论分析和Kyoto基因与基因组途径的重叠分析。通过分析,我们发现在老年中,男性和女性的炎症和细胞外基质(ECM)相关基因和通路均上调,老年雄性比老年雌性更明显。此外,定量实时PCR分析证实,肿瘤坏死因子(TNF)信号相关基因Birc3、Socs3和Tnfrsf1b,以及ECM相关基因Cd44、Col3a1和Col5a2的表达在老年雄性而非雌性中显著上调。同时,组织学分析的伊红染-苏木染(H&E)染色表明,老年雄性表现出较老年雌性更严重的肾损伤。总之,大鼠肾脏中,TNF信号和ECM积累相关的基因在雄性中的上调程度高于女性,在衰老过程中可能对肾脏炎症和纤维化产生更大影响。
Aging leads to the functional decline of an organism, which is associated with age and sex. To understand the functional change of kidneys depending on age and sex, we carried out a transcriptome analysis using RNA sequencing (RNA-Seq) data from rat kidneys. Four differentially expressed gene (DEG) sets were generated according to age and sex, and Gene Ontology analysis and overlapping analysis of Kyoto Encyclopedia of Genes and Genomes pathways were performed for the DEG sets. Through the analysis, we revealed that inflammation- and extracellular matrix (ECM)-related genes and pathways were upregulated in both males and females during aging, which was more prominent in old males than in old females. Furthermore, quantitative real-time PCR analysis confirmed that the expression of tumor necrosis factor (TNF) signaling-related genes, Birc3, Socs3, and Tnfrsf1b, and ECM-related genes, Cd44, Col3a1, and Col5a2, which showed that the genes were markedly upregulated in males and not females during aging. Also, hematoxylin-eosin (H&E) staining for histological analysis showed that renal damage was highly shown in old males rather than old females. In conclusion, in the rat kidney, the genes involved in TNF signaling and ECM accumulation are upregulated in males more than in females during aging. These results suggest that the upregulation of the genes may have a higher contribution to age-related kidney inflammation and fibrosis in males than in females.