OBJECTIVE: The present study investigated the relationships between reactive oxygen species (ROS), interstitial fibrosis, and renal proximal tubular cell (RPTC) apoptosis in type 2 diabetic db/db mice and in db/db transgenic (Tg) mice overexpressing rat catalase (rCAT) in their RPTCs (db/db rCAT-Tg). RESEARCH DESIGN AND METHODS: Blood pressure, blood glucose, and albuminuria were monitored for up to 5 months. Kidneys were processed for histology and apoptosis studies (terminal transferase-mediated dUTP nick-end labeling or immunostaining for active caspase-3 and Bax). Real-time quantitative PCR assays were used to quantify angiotensinogen (ANG), p53, and Bax mRNA levels. RESULTS: db/db mice developed obesity, hyperglycemia, hypertension, and albuminuria. In contrast, db/db rCAT-Tg mice became obese and hyperglycemic but had normal blood pressure and attenuated albuminuria compared with db/db mice. Kidneys from db/db mice displayed progressive glomerular hypertrophy, glomerulosclerosis, interstitial fibrosis, and tubular apoptosis and increased expression of collagen type IV, Bax, and active caspase-3, as well as increased ROS production. These changes, except glomerular hypertrophy, were markedly attenuated in kidneys of db/db rCAT-Tg mice. Furthermore, ANG, p53, and Bax mRNA expression was increased in renal proximal tubules of db/db mice but not of db/db rCAT-Tg mice. CONCLUSIONS: Our results indicate a crucial role for intra-renal ROS in the progression of hypertension, albuminuria, interstitial fibrosis, and tubular apoptosis in type 2 diabetes and demonstrate the beneficial effects of suppressing ROS formation.
OBJECTIVE: The present study investigated the relationships between reactive oxygen species (ROS), interstitial fibrosis, and renal proximal tubular cell (RPTC) apoptosis in type 2 diabetic db/db mice and in db/db transgenic (Tg) mice overexpressing rat catalase (rCAT) in their RPTCs (db/db rCAT-Tg). RESEARCH DESIGN AND METHODS: Blood pressure, blood glucose, and albuminuria were monitored for up to 5 months. Kidneys were processed for histology and apoptosis studies (terminal transferase-mediated dUTP nick-end labeling or immunostaining for active caspase-3 and Bax). Real-time quantitative PCR assays were used to quantify angiotensinogen (ANG), p53, and Bax mRNA levels. RESULTS: db/db mice developed obesity, hyperglycemia, hypertension, and albuminuria. In contrast, db/db rCAT-Tg mice became obese and hyperglycemic but had normal blood pressure and attenuated albuminuria compared with db/db mice. Kidneys from db/db mice displayed progressive glomerular hypertrophy, glomerulosclerosis, interstitial fibrosis, and tubular apoptosis and increased expression of collagen type IV, Bax, and active caspase-3, as well as increased ROS production. These changes, except glomerular hypertrophy, were markedly attenuated in kidneys of db/db rCAT-Tg mice. Furthermore, ANG, p53, and Bax mRNA expression was increased in renal proximal tubules of db/db mice but not of db/db rCAT-Tg mice. CONCLUSIONS: Our results indicate a crucial role for intra-renal ROS in the progression of hypertension, albuminuria, interstitial fibrosis, and tubular apoptosis in type 2 diabetes and demonstrate the beneficial effects of suppressing ROS formation.
Authors: Marie-Luise Brezniceanu; Cara J Lau; Nicolas Godin; Isabelle Chénier; Alain Duclos; Jean Ethier; Janos G Filep; Julie R Ingelfinger; Shao-Ling Zhang; John S D Chan Journal: J Am Soc Nephrol Date: 2010-03-18 Impact factor: 10.121
Authors: Shuiling Zhao; Anindya Ghosh; Chao-Sheng Lo; Isabelle Chenier; James W Scholey; Janos G Filep; Julie R Ingelfinger; Shao-Ling Zhang; John S D Chan Journal: Endocrinology Date: 2018-02-01 Impact factor: 4.736