Renoprotective effect of Stat1 deletion in murine aristolochic acid nephropathy.

Injured tubule epithelium stimulates a pro-fibrotic milieu that accelerates loss of function in chronic kidney disease (CKD). This study tested the role of STAT1 in the progressive loss of kidney function in aristolochic acid (AA) nephropathy, a model of CKD. Mean serum creatinine concentration increased in wild type (WT) littermates treated with AA, while Stat1-/- mice were protected. Focal increases in the apical expression of Kidney Injury Molecule (KIM)-1 were observed in the proximal tubules of WT mice with AA treatment, but was absent in Stat1-/- mice in the treatment group as well as in both control groups. A Composite Injury Score, an indicator of proximal tubule injury, was reduced in Stat1-/- mice treated with AA. Expression of integrin β6 and p-Smad2/3 in proximal tubules and interstitial collagen and fibronectin were observed in WT mice following AA treatment, but were all decreased in AA-treated Stat1-/- mice. The data indicated that STAT1 activation facilitated the development of progressive kidney injury and interstitial fibrosis in AA nephropathy.