作者
Fan Fan, Aron M Geurts, Mallikarjuna R Pabbidi, Ying Ge, Chao Zhang, Shaoxun Wang, Yedan Liu, Wenjun Gao, Ya Guo, Longyang Li, Xiaochen He, Wenshan Lv, Yoshikazu Muroya, Takashi Hirata, Jeremy Prokop, George W Booz, Howard J Jacob, Richard J Roman
发表日期
2020/4/1
期刊
Journal of the American Society of Nephrology
卷号
31
期号
4
页码范围
687-700
出版商
LWW
简介
Background
The genes and mechanisms involved in the association between diabetes or hypertension and CKD risk are unclear. Previous studies have implicated a role for γ-adducin (ADD3), a cytoskeletal protein encoded by Add3.
Methods
We investigated renal vascular function in vitro and in vivo and the susceptibility to CKD in rats with wild-type or mutated Add3 and in genetically modified rats with overexpression or knockout of ADD3. We also studied glomeruli and primary renal vascular smooth muscle cells isolated from these rats.
Results
This study identified a K572Q mutation in ADD3 in fawn-hooded hypertensive (FHH) rats—a mutation previously reported in Milan normotensive (MNS) rats that also develop kidney disease. Using molecular dynamic simulations, we found that this mutation destabilizes a critical ADD3-ACTIN binding site. A reduction of ADD3 expression in membrane fractions prepared from …
学术搜索中的文章
F Fan, AM Geurts, MR Pabbidi, Y Ge, C Zhang, S Wang… - Journal of the American Society of Nephrology, 2020
