Figure 3.

Proximal tubule-specific loss of Sirt6 increases UUO-induced myofibroblast activation. (A) Representative sections of kidneys from sham- and UUO-operated Sirt6^flox/flox; Ggt1-Cre^- (WT) and Sirt6^flox/flox; Ggt1-Cre⁺ (PT-Sirt6KO) mice were immunofluorescence stained with α-SMA and FSP-1 (red). The nucleus was stained by DAPI (blue). Scale bar = 50 μm. The bar graph shows area fractions of α-SMA (%) and the number of FSP-1 (+) cells in the sham- and UUO-operated kidneys from ten randomly chosen, non-overlapping fields at a magnification of 400× (n = 15 per group). (B) Representative Western blot analysis of α-SMA expression in the kidneys from sham- and UUO-operated Sirt6^flox/flox; Ggt1-Cre^- (WT) and Sirt6^flox/flox; Ggt1-Cre⁺ (PT-Sirt6KO) mice. The bar graph shows the densitometric quantification presented as the relative ratio of each protein to β-actin. The relative ratio measured in the kidneys from sham-operated WT mice is arbitrarily presented as 1. Data are expressed as mean ± SD. ***, p < 0.001 versus WT sham or PT-Sirt6KO sham; ###, p < 0.001 versus WT UUO. Sham, sham-operated mice; UUO, unilateral ureteral obstruction; WT, wild-type; PT-Sirt6KO, proximal tubule-specific Sirt6 knockout; α-SMA, α-smooth muscle actin; FSP-1, fibroblast-specific protein-1; DAPI, 4′,6-diamidino-2-phenylindole.