Fig 2: The pathway analysis of GADD45A, GADD45B, and co-expression genes in renal ischemia-reperfusion injury (IRI). (A) Three clusters in the protein–protein interaction network. The corresponding proteins of intersected genes were divided into three clusters in a protein–protein interaction network using the k-means method. (B) The KEGG pathways analysis of cluster 1 co-expression genes, including GADD45A and GADD45B.

Fig 3: The correlation analysis of GADD45A and GADD45B expression with cell surface markers of plasmacytoid dendritic cells (pDCs) in human renal ischemia-reperfusion injury (IRI). (A) The significant relationship of GADD45A expression with cell surface markers (CLEC4C and NRP1) of pDCs. (B) The significant association of GADD45B expression with cell surface marker (IRF8) of pDCs. (C) The representative immunofluorescence pictures of GADD45A (red), BST2 (green), and DAPI (blue) are shown in sham-operated mice and renal IRI mice, GADD45A+BST2+ pDCs (white arrows), scale bars (white) = 50 µm. (D) The representative immunofluorescence pictures of GADD45B (red), BST2 (green), and DAPI (blue) are shown in sham-operated mice and renal IRI mice, GADD45B+BST2+ pDCs (white arrows), scale bars (white) = 50 µm. (E) The number of GADD45A+BST2+ and (F) GADD45B+BST2+ pDCs in the kidney tissue was counted, n = 4 per group. (G) The gene-to-gene network analysis of GADD45A, GADD45B, and pDC cell markers was constructed using the Metascape website and GeneMANIA online tool. MAPK pathways and type I interferon responses were identified. CLEC4C, C-Type Lectin Domain Family 4 Member C; NRP1, Neuropilin 1; IRF, Interferon Regulatory Factor 8; BST2, Bone Marrow Stromal Cell Antigen 2. ** p < 0.01.

Fig 4: Interaction network showing the potential treatments for renal ischemia-reperfusion injury, GADD45A, GADD45B, and related microRNAs (miRs). The white circles represent the 3D structure tomographs of predicted drugs, while the white ovals represent the related miRs.

Fig 5: The construction and validation of a chromatin regulator (CR)-associated predictive human renal ischemia-reperfusion injury (IRI) risk score nomogram. (A) The protein–protein interaction (PPI) network of the five intersection genes. (B) Receiver operator characteristic (ROC) curve of the predictive IRI risk model in the training cohort. (C) Validation of GADD45A and GADD45B expression and (D) the predictive IRI risk model in the merged datasets of human GSE30718 and GSE126805 (validation cohort). GADD45A (growth arrest and DNA damage inducible protein 45 alpha); GADD45B (growth arrest and DNA damage inducible protein 45 beta). * p < 0.05, *** p < 0.001.