Figure 3.
Myeloid IRF4 deletion led to relatively better kidney function and decreased renal fibrosis 4 weeks after AKI. Male IRF4f/f (WT) and LysM-Cre IRF4f/f (MΦ IRF4−/−) mice underwent AKI and were sacrificed 4 weeks later. (A and B) MΦ IRF4−/− mice had lower serum creatinine and albuminuria (A) and less tubular injury (B). *P<0.05, **P<0.01, ***P<0.001, n=9 in (A) and n=4 in (B). (C) MΦ IRF4−/− mice had less renal fibrosis as indicated by Sirius red staining. Original magnification ×160. ***P<0.001, n=6. (D) Quantitative PCR analysis showed decreases in renal mRNA levels of profibrotic and fibrotic components, including TGF-β1, TGF-β2, α-SMA, CTGF, collagen I (col I), col III, col IV, and fibronectin (FN) in MΦ IRF4−/− mice. **P<0.01, ***P<0.001; n=7 in WT group and n=8 in MΦ IRF4−/− group. (E) Immunoblotting showed decreased renal protein levels of α-SMA and CTGF in MΦ IRF4−/− mice. **P<0.01, n=4 in WT group and n=5 in MΦ IRF4−/− group. (F) Immunostaining showed that MΦ IRF4−/− mice had decreased renal expression of profibrotic and fibrotic components, including col I, col IV, α-SMA (marker of myofibroblasts), and CTGF. Original magnification ×160 for all. *P<0.05, **P<0.01, ***P<0.001, n=4 for all.