Figure 4.

Transgenic overexpression of 15-lipoxygenase (15-LO) reverses the anti-inflammatory, antifibrotic phenotype observed in knockout animals after unilateral ureteral obstruction (UUO). 15-LO transgenic overexpressing (15LOTG) mice and wild-type (WT) mice were subjected to UUO, and kidneys were collected at 14 days (d) as previously described. A: percent weight changes between WT and 15LOTG mice, quantification of picrosirius red (PSR) polarized images, quantification of F4/80 immunostained images, and hydroxyproline assessment normalized to total protein. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 by one-way ANOVA. B: representative PSR-stained specimens from 14-day UUO kidneys with respective polarized images at ×20 magnification, indicating worsening of fibrosis and inflammation in 15LOTG mice. C: quantitative RT-PCR was performed on separate animals, and animals were euthanized 10 days after UUO. 15-LO overexpression increased transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), and chemokine (C-X3-C motif) ligand 1 (CX3CL1) expression but did not change tumor necrosis factor-α (TNF-α) expression and diminished chemokine (C-C motif) ligand 2 (CCL2) expression. *P < 0.05, **P < 0.01, and ***P < 0.001 by one-way ANOVA. IHC, immunohistochemistry; ns, not significant.