*2.2. SH045 Treatment Does Not Alter Kidney Parenchymal Damage*

Morphologically, UUO increased mesangial matrix deposition, leading to glomerular hypertrophy, and tubular dilatation (Figure 2A–D). The expressions of renal damage markers, kidney injury molecule-1 (*Havcr1*) and Lipocalin-2 (*Lcn2*), were increased in UUO kidneys compared to control (Figure 2E,F). However, SH045 did not affect these parameters in both UUO and control kidneys (Figure 2A–F). These results indicate that TRPC6 inhibition per se has no impact on the damage to renal parenchyma (glomerular or tubular) caused by UUO.

**Figure 2.** SH045 impact on kidney histopathology after UUO. (**A**) Representative images of UUOinjured glomerulus (magnification: 400×). Kidney sections were stained with periodic acid–Schiff staining (PAS). (**B**) Quantification of glomerular damage (control *n* = 6, UUO *n* = 8). (**C**) Representative images of UUO-injured tubules (magnification: 400×). Kidneys sections were stained with periodic acid–Schiff staining (PAS). Arrows indicate tubular injury. Scale bars are 50 μm. (**D**) Semi-quantification of tubular damage (control *n* = 6, UUO *n* = 8). (**E**) Renal mRNA levels of kidney injury molecule 1 (*Havcr1*) and (**F**) Lipocalin 2 (*Lcn2*) (control *n* = 10, UUO *n* = 11). Data expressed as means ± SD. Two-way ANOVA followed by Sidak's multiple comparisons post hoc test. \* *p* < 0.05, \*\*\* *p* < 0.001 and \*\*\*\* *p* < 0.0001 defined as significant. ns, not statistically significant. AU, arbitrary units.
