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

• Published in: Biological & pharmaceutical bulletin Vol. 46; no. 4; pp. 552 - 562
• Main Authors: Noh, Sang Gyun, Jung, Hee Jin, Kim, Seungwoo, Arulkumar, Radha, Chung, Ki Wung, Park, Daeui, Choi, Yeon Ja, Chung, Hae Young
• Format: Journal Article
• Language: English
• Published: Japan Japan Science and Technology Agency 01-04-2023
• Subjects: Aging; Animals; CD44 antigen; Extracellular matrix; Extracellular Matrix - genetics; Females; Fibrosis; Gene expression; Gene Expression Profiling; Genes; Genomes; Inflammation; Kidney; Kidneys; Male; Males; Rats; Sex; Sex Characteristics; Sex differences; Signal transduction; Transcriptome; Transcriptomes; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumor Necrosis Factors - metabolism; kidney; extracellular matrix accumulation; aging; sex difference; inflammation
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b22-00601

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.