Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes.
Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN). Endoplasmic reticulum (ER) stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA) is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p.) twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology. These changes were associated with a significant decreased expression of ER stress markers. At the same time, diabetic db/db mice had more TUNEL-positive nuclei in the renal tubule, which were attenuated by TUDCA treatment, along with decreases in ER stress-associated apoptotic markers in the kidneys. In summary, the effect of TUDCA on tubular injury, in part, is associated with inhibition of ER stress in the kidneys of diabetic db/db mice. TUDCA shows potential as a therapeutic target for the prevention and treatment of DN.
Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. jingzhang721@163.com.
Jing
J
Zhang
Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. fanyingsh@126.com.
Ying
Y
Fan
Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. zengchuchu1991@yahoo.com.
Chuchu
C
Zeng
Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. 12211280018@fudan.edu.cn.
Li
L
He
Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. wangniansong2008@163.com.
Niansong
N
Wang
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D004721:Endoplasmic Reticulum; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D013312:Stress, Physiological; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
D015415:Biomarkers; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine
apoptosis; diabetic nephropathy; endoplasmic reticulum stress; tauroursodeoxycholic acid
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