Attenuation of interstitial fibrosis and tubular apoptosis in db/db transgenic mice overexpressing catalase in renal proximal tubular cells
Attenuation of interstitial fibrosis and tubular apoptosis in db/db transgenic mice overexpressing catalase in renal proximal tubular cells
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DOI：
10.2337/db07-0013
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发表时间：
2008-02-01
期刊：
影响因子：
7.7
通讯作者：
Chan, John S. D.
中科院分区：
文献类型：
--
作者：
Brezniceanu, Marie-Luise;Liu, Fang;Chan, John S. D.
本研究调查了2型糖尿病db/db小鼠和在其RPTC中过表达大鼠过氧化氢酶（rCAT）的db/db转基因（Tg）小鼠（db/db rCAT-Tg）中活性氧（ROS）、间质纤维化和肾近端小管细胞（RPTC）凋亡之间的关系。研究设计和方法：监测血压、血糖和蛋白尿长达5个月。对肾脏进行组织学中期凋亡研究（末端转移酶介导的dUTP缺口末端标记或活性半胱天冬酶-3和Bax的免疫染色）。实时定量PCR检测血管紧张素原（ANG）、p53和Bax mRNA的表达水平。相比之下，db/db rCAT-Tg小鼠变得肥胖和高血糖，但与db/db小鼠相比，血压正常，白蛋白尿减少。db/db小鼠的肾脏表现出进行性肾小球肥大、肾小球硬化、间质纤维化和肾小管凋亡，TV型胶原、Bax和活性半胱天冬酶-3的表达增加，以及ROS产生增加。除了肾小球肥大外，这些变化在db/db rCAT-Tg小鼠的肾脏中显著减弱。此外，ANG，p53，Bax mRNA的表达增加，在肾近端小管的db/db小鼠，但不是db/db rCAT-Tg mice. CONCLUSIONS-我们的研究结果表明，肾内ROS在高血压，白蛋白尿，间质纤维化，肾小管细胞凋亡的进展在2型糖尿病的关键作用，并证明抑制ROS形成的有益影响。
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 mid 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 TV, 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 intrarenal 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.