Fig 2: The upregulation of Cdc42 in podocytes increased the Cdc42 expression and the p-p38/p38 ratio in β-TC6 cells, which were accompanied by an increase in malondialdehyde (MDA) levels and a decrease in SOD activity. (A–C) The protein expression levels of Cdc42, p-38, and p-p38 in β-TC6 cells were detected. (D–G) The levels of MDA and SOD in MPC5 cells and β-TC6 cells were measured. Data are presented as mean ± SEM; *P < 0.05.

Fig 3: Gsα deletion downregulated BMP-mediated signaling and cAMP/CREB1 signaling.A Heat map representing differentially expressed genes between GsαCMKO mice and control mice B Gene ontology analysis of differentially expressed genes C KEGG analysis of top ten enriched pathways D Quantitative analysis of the mRNA expression of differentially expressed genes involving Acta1, Nppa, Nppb, Myh7, Creb1, and Bmp10, n = 3 per group E Western blot analysis of protein level of total CREB1, p-CREB1 (at ser-133), and PKA between GsαCMKO mice and control mice. F Quantitative analysis of the expression of CREB1/GAPDH, p-CREB1/GAPDH, and PKA/GAPDH, n = 3 per group G Western blot analysis of key signaling molecules of Bmp10-mediated Smad-dependent signaling at between GsαCMKO mice and control mice. H Quantitative analysis of the expression of Bmp10/GAPDH, p-Smad1/5/8 (at Ser463/Ser465/Ser467)/GAPDH, Type I collagen/GAPDH, and Type III collagen/GAPDH, n = 3 per group I Western blot analysis of key signaling molecules of Bmp10-mediated Smad-independent signaling between GsαCMKO mice and control mice. Including Stat3, p-Stat3 (at Tyr705), p-AKT (at Ser473), AKT, p-P38 (at Thr180/Tyr182), and P38. J Quantitative analysis of the expression of p-AKT/total AKT, p-P38/total P38, n = 3 per group. Mean ± SEM, *p < 0.05, **p < 0.01, ****p < 0.0001 vs control group. Statistical analysis was carried out by a two-tailed Student’s t-test.

Fig 4: RAGRP3 is a downstream effector molecule of AC092894.1. A Volcano plot of differentially expressed genes obtained by RNA-seq. B KEGG pathway analysis for AC092894.1. The vertical axis represents the pathway. The horizontal axis represents enrichment factors. The size of the dots indicates the number of differentially expressed genes in the corresponding pathway (gene count). The color of the dots indicates the specific value of P-value. C Western blotting to detect the expression of p38 and p-p38 in cell lysates, with α-Tubulin as a control. D RT-qPCR for expression of MAPK signaling pathway-related molecules in LoVo-OxR after overexpression of AC092894.1. E Western blotting to detect the expression of ATF2 and RASGRP3 in cell lysates, with GAPDH was as a control. F Expression of AC092894.1 in our cohort of CRC patients sensitive (n = 28) and resistant (n = 22) to oxaliplatin treatment

Fig 5: AC098894.1 promotes oxaliplatin sensitization of drug-resistant CRC cells in vivo. A Nude mice were subcutaneously xenografted with HCT116-OxR cells (4 × 106 cells) and injected intraperitoneally with oxaliplatin (5 mg/kg/day per mouse) or DMSO every 5 days. B Tumor weighing analysis. C Tumor growth curves for each group. Data were subjected to Student’s t-test. D RT-qPCR assays for the expression of AC092894.1 in each group of tumors. E Representative IHC images showing p-p38 expression in tumors from each group of mice