title: Endoplasmic Reticulum Chaperon Tauroursodeoxycholic Acid Attenuates Aldosterone-Infused Renal Injury.
abstract: Aldosterone (Aldo) is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER) stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA), and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-βexpression, as well as the downregulation of the expression of Nlrp3 inflammasome markers, Nlrp3, ASC, IL-1β, and IL-18. This paper presents an important role for ER stress on the renal inflammatory response to Aldo. Additionally, the inhibition of ER stress by TUDCA negatively regulates the levels of these inflammatory molecules in the context of Aldo.
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Guo
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
authors.forename: Lilu
authors.initials: L
authors.lastname: Ling
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
authors.forename: Yong
authors.identifier: 0000-0001-7336-513X
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Division of Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai 200011, China.
authors.forename: Wei
authors.identifier: 0000-0002-6450-1635
authors.initials: W
authors.lastname: Ding
mesh_terms: D000450:Aldosterone / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007668:Kidney / Q000187:drug effects* / Q000293:injuries*; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013655:Taurochenodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D017382:Reactive Oxygen Species; D000450:Aldosterone; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine