PA-S14 protects against renal fibrosis and tubular cell senescence in UIRI mice. (A) The heatmap, generated from the RNA-seq analysis, showing cellular senescence, Wnt/β-catenin signaling pathway and collagen fibril organization gene expression in UIRI and UIRI/PA-S14 groups. (B-F) Representative western blot and quantitative data showing renal expression of active-β-catenin, p16INK4A, Klotho and KIM-1. Numbers (1-3) indicate each individual animal in a given group. **P < 0.01, ***P < 0.001 versus sham controls; ##P < 0.01, ###P < 0.001 versus UIRI (n = 5). (G) Representative micrographs show the expression of active β-catenin, Klotho, KIM-1, and SA‐β‐gal activity in different groups as indicated. Frozen kidney sections were stained for active β-catenin expression and SA‐β‐gal activity. Paraffin sections were stained with antibodies against Klotho and KIM-1, respectively. Arrows indicate positive staining. Scale bar, 50 µm. (H-I) Representative western blot and quantitative data show the reduction of renal Fibronectin, Collagen I, and α‐SMA expression after PA-S14 treatment. Numbers (1-3) indicate each individual animal in given group. **P < 0.01, ***P < 0.001 versus sham controls; ##P < 0.01, ###P < 0.001 versus UIRI (n = 5). (J) Representative staining micrographs show Sirius red staining, and renal expression of Fibronectin and α‐SMA. Paraffin sections were performed to Sirius red staining or immunostained with antibodies against Fibronectin and α‐SMA. Arrows indicate positive staining. Scale bar, 50 µm. (K) Graphical representations of the degree of fibrotic lesions in different groups after quantitative determination of Sirius red staining intensity. ***P < 0.001 versus sham controls; ###P < 0.001 versus UIRI (n = 5). (L) Urinary albumin levels in different groups. Urinary albumin was expressed as milligrams per milligram creatinine. **P < 0.01 versus sham controls; ##P < 0.01 versus UIRI (n = 5). (M-N) The treatment of PA-S14 significantly decreased serum creatinine and BUN levels. **P < 0.01, ***P < 0.001 versus sham controls; ##P < 0.01, ###P < 0.001 versus UIRI (n = 5).