Open AccessRenoprotective effect of Stat1 deletion in murine aristolochic acid nephropathy
Author(s) -
Wei Feng,
WeiZhong Ying,
Xingsheng Li,
Lisa M. Curtis,
Paul W. Sanders
Publication year - 2021
Publication title -
american journal of physiology. renal physiology./american journal of physiology. renal physiology
Language(s) - English
Resource type - Journals
eISSN - 1931-857X
pISSN - 1522-1466
DOI - 10.1152/ajprenal.00401.2020
Subject(s) - aristolochic acid , stat1 , renal function , creatinine , kidney , nephropathy , kidney disease , medicine , stat protein , endocrinology , fibronectin , chemistry , biology , apoptosis , biochemistry , receptor , stat3 , diabetes mellitus , genetics , extracellular matrix
Injured tubule epithelium stimulates a profibrotic milieu that accelerates loss of function in chronic kidney disease (CKD). This study tested the role of signal transducer and activator of transcription 1 (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, whereas 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 were 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. Increased expression of integrin-β 6 and phosphorylated Smad2/3 in proximal tubules as well as 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.