Abstract: 【Abstract】 Objective To investigate the potential molecular mechanism underlying hydronephrosis induced by ureteropelvic junction obstruction (UPJO) in children. Method Differential expression analysis was conducted between the UPJO group and the control group in the GSE96101 and GSE96102 datasets, followed by co-expression analysis of the intersected differentially expressed gene (DEG). Enrichment analysis was performed on the genes of the module with the highest correlation to UPJO and obstruction duration, further identifying obstruction-related genes from the signaling pathway genes. From June 2021 to October 2023, hydronephrosis tissue and marginally normal control kidney tissue samples, as well as urine samplesbefore and after surgery from children with UPJO were collected. The expression of obstruction-related genes was detected using real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blotting, and the expression of inflammatory factors was detected using enzymelinkedimmunosorbent assay (ELISA). The UPJO rat model was established, and kidney tissue sampleswere collected from the control group, and one, two, and four weeks after surgery, respectively. The levelof renal fibrosis was detected using Masson staining, and the expression of obstruction-related genes wasdetected using RT-qPCR and Western blotting. Immunohistochemistry was used to detect the expression of Myb and Raf1. Statistical methods performed by one-way ANOVA analysis and t-test. Result Atotal of 3 524 intersected DEG were identified from the GSE96101 and GSE96102 datasets, and 10 coexpression modules were constructed. The Lightgreen module had the highest correlation with UPJO, and the blue module had the highest correlation with obstruction duration. Genes in the Lightgreen module were mainly enriched in the C-type lectin receptor signaling pathway, while genes in the blue module were mainly enriched in the phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/Akt) signaling pathway. The LASSO model results showed that Myb and Egfr in the PI3K/Akt signaling pathway had the highest importance, and Raf1 and Relb in the C-type lectin receptor signaling pathway had the greatest fold change in differential expression. Compared with the normal control tissue, Myb, Egfr, Raf1 and Relb were significantly overexpressed in hydronephrosis tissue (P<0.001). Interleukin-6 (IL-6), monocyte chemotactic protein-1(MCP-1), neutrophil gelatinase-associated lipocalin (NAGL) were significantly increased in urine samples from children with UPJO (P<0.001). Compared with the control group, the degree of kidney tissue fibrosis increased in UPJO rats after surgery. The expression of Myb, Egfr, Raf1 and Relb gradually increased with time after surgery in UPJO rats (P<0.001). Conclusion Abnormal activation of PI3K/Akt and C-type lectin receptor signaling pathways may be a potential molecular mechanism of hydronephrosis induced by UPJO, and the increased expression of MYB, EGFR, RAF1 and RELB may be related to the progression of hydronephrosis in children with UPJO.
2025, Vol. 13 
