Figure 4. Myofibroblast-specific YAP/TAZ deficiency attenuates unilateral ureteral obstruction–induced kidney fibrosis.

Myofibroblast-specific YAP/TAZ-deficient mice (Col1a1-Cre/ERT^+/– Yap^fl/fl Taz^fl/fl) and their WT littermates (Col1a1-Cre/ERT^–/– Yap^fl/fl Taz^fl/fl) were randomized to sham surgery (n = 3 Col1a1-Cre/ERT^+/– Yap^fl/fl Taz^fl/fl and n = 5 Col1a1-Cre/ERT^–/– Yap^fl/fl Taz^fl/fl) or left-sided unilateral ureteral obstruction (n = 12 Col1a1-Cre/ERT^+/– Yap^fl/fl Taz^fl/fl and n = 7 Col1a1-Cre/ERT^–/– Yap^fl/fl Taz^fl/fl). Tamoxifen was administered between days 0 and 6 after surgery to activate expressed Cre recombinase. Left kidneys were harvested 7 days after surgery. (A) Kidney sections were stained with antibodies directed against α-smooth muscle actin (α-SMA), YAP, or TAZ, and nuclei were counterstained with DAPI to assess for successful YAP and TAZ excision in myofibroblasts. White arrows depict α-SMA⁺ cells expressing YAP. White arrowheads depict α-SMA⁺ cells without significant YAP expression. Note the lack of red YAP and TAZ staining in myofibroblasts of YAP/TAZ-KO animals (Col1a1-Cre/ERT^+/– Yap^fl/fl Taz^fl/fl). White scale bar: 10 μm. Kidney sections were next stained with (B) picrosirius red (PSR) to label fibrillar collagen, (C) Masson’s trichrome to stain extracellular matrix, or (D) an antibody directed against α-SMA. Black scale bar: 100 μm. One-way ANOVA with post hoc Tukey’s test was used for comparisons. Data shown as mean ± SEM. *P < 0.05.