We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Nrf2-deficient female mice develop lupus-like autoimmune nephritis<sup>1</sup>.
- Authors
Yoh, Keigyou; Itoh, Ken; Enomoto, Akiko; Hirayama, Aki; Yamaguchi, Naoto; Kobayashi, Masaki; Morito, Naoki; Koyama, Akio; Yamamoto, Masayuki; Takahashi, Satoru
- Abstract
Nrf2-deficient female mice develop lupus-like autoimmune nephritis. Background. NF-E2–related factor 2 (Nrf2) is a basic leucine zipper transcriptional activator essential for the coordinate transcriptional induction of antioxidant enzymes and phase II drug metabolizing enzymes through the antioxidant response element/electrophile response element. The Nrf2-deficient mice were found to develop normally under standard laboratory conditions. However, upon closer examination, we found that aged female Nrf2-deficient mice displayed a shortened lifespan and developed severe glomerulonephritis. The present study investigated the glomerulonephritis findings in Nrf2-deficient mice. Methods. To evaluate glomerular lesions of Nrf2-deficient mice, histological and functional analyses were performed. The amounts of serum immunoglobulins, anti-double-stranded (ds) DNA antibody, and lipid peroxidation using thiobarbituric acid reactive substances (TBARS) also were measured. Results. Nrf2-deficient female mice over 60 weeks of age developed severe nephritis characterized by cellular proliferation, lobular formation, crescent formation, and subepithelial electron-dense deposits. In immunofluorescent assays, Nrf2-deficient female mice showed mesangial deposits and massive granular deposits of IgG, IgM, and C3 along the capillary walls. Higher serum levels of IgG, anti-dsDNA antibody, lower creatinine clearance, and slight splenomegaly also were found in Nrf2-deficient female mice. A higher concentration of TBARS also was found in Nrf2-deficient female mice. Conclusions. These data indicate that the aged Nrf2-deficient female mice develop lupus-like autoimmune nephritis and suggest that nrf2 is one of the genes determining susceptibility to autoimmune disease. Analysis of nephritis in the Nrf2-deficient female mouse may clarify the mechanisms leading to the development of lupus disease.
- Subjects
GLOMERULONEPHRITIS; KIDNEY diseases; AUTOIMMUNE diseases
- Publication
Kidney International, 2001, Vol 60, Issue 4, p1343
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2001.00939.x