GSPE Inhibits HMGB1 Release, Attenuating Renal IR-Induced Acute Renal Injury and Chronic Renal Fibrosis.
Grape seed proanthocyanindin extract (GSPE) is a polyphenolic bioflavonoid derived from grape seeds and has been widely studied for its potent antioxidant, anti-inflammatory and antitumor activities. HMGB1 is a newly discovered danger-associated molecular pattern (DAMP) that has potent proinflammatory effects once released by necrotic cells. However, the effect of GSPE on the HMGB1, and the relationship of those two with acute kidney injury and chronic kidney fibrosis are unknown. This study aimed to investigate the impact of GSPE on acute kidney injury and chronic fibrosis. C57bl/6 mice were subjected to bilateral ischemia/reperfusion (I/R) and unilateral I/R with or without GSPE administration. After bilateral I/R, mice administered GSPE had a marked improvement in renal function (BUN and Cr), decreased pathological damage and reduced inflammation. In unilateral I/R, mice subjected GSPE showed reduced tubulointerstitial fibrosis and decreased inflammatory reaction. The renoprotection of GSPE on both models was associated with the inhibition of HMGB1 nucleocytoplasmic shuttling and release, which can amplify the inflammation through binding to its downstream receptor TLR4 and facilitated P65 transcription. Thus, we have reason to believe that GSPE could be a good alternative therapy for the prevention and treatment of IR-induced renal injury and fibrosis in clinical practice.
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. zhan021989juan@foxmail.com.
Juan
J
Zhan
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. wangkun901109@163.com.
Kun
K
Wang
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. yaoyaoyouxin@outlook.com.
Conghui
C
Zhang
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. zhangchunxiu03@163.com.
Chunxiu
C
Zhang
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. wuanliyue@126.com.
Yueqiang
Y
Li
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. zhangying19880914@163.com.
Ying
Y
Zhang
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. yanloveiy666@163.com.
Xiaoyan
X
Chang
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. qiaodanzhou_1000@163.com.
Qiaodan
Q
Zhou
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. yaoyingkk@126.com.
Ying
Y
Yao
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. liuyy1919@163.com.
Yanyan
Y
Liu
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China. xugang@tjh.tjmu.edu.cn.
Gang
G
Xu
GSPE; HMGB1; acute kidney injury; chronic kidney fibrosis
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