| FXR agonist GW4064 reduces sepsis-induced inflammation and acute kidney injury in mice |
| Received:December 01, 2021 Revised:March 22, 2022 Click here to download the full text |
| Citation of this paper:REN Ting,XU Su-juan,WANG Xiao-yan,ZOU Zhou-ping,DING Xiao-qiang,JIA Ping.FXR agonist GW4064 reduces sepsis-induced inflammation and acute kidney injury in mice[J].Chinese Journal of Clinical Medicine,2022,29(3):365-371 |
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| Author Name | Affiliation | E-mail | | REN Ting | Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China | | | XU Su-juan | Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China | | | WANG Xiao-yan | Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China | | | ZOU Zhou-ping | Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China | | | DING Xiao-qiang | Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Kidney and Dialysis Institute of Shanghai, Shanghai 200032, China
Kidney and Blood Purification Laboratory of Shanghai, Shanghai 200032, China | | | JIA Ping | Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Kidney and Dialysis Institute of Shanghai, Shanghai 200032, China
Kidney and Blood Purification Laboratory of Shanghai, Shanghai 200032, China | jia.ping1@zs-hospital.sh.cn |
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| Abstract:Objective To explore the effect of farnesoid X receptor (FXR) on lipopolysaccharide (LPS)-induced inflammation and acute kidney injury (AKI) via sepsis model in vivo and in vitro. Methods Mouse sepsis model was established through LPS administration, and the experimental animals were randomly divided into four groups:normal saline (NS) group, LPS group, LPS+DMSO group, and LPS+GW4064 group. Each group contained 5-8 mice. Mice in LPS group were intraperitoneally injected with LPS at a dose of 10 mg/kg, and mice in NS group were injected with the equal volume of saline. The latter two groups were injected consecutively with GW4064 or vehicle for 5 days before LPS injection. Blood and kidney tissue were collected 24 hours after LPS injection to detect renal function and inflammatory factor expression. Primary tubular epithelial cells (PTECs) were isolated and treated with LPS in vitro and divided into four groups:NS group, LPS group, LPS+DMSO group, LPS+GW4064 group. The expression of proinflammatory factors was determined by RT-PCR. Results Compared with NS group, the expression of renal pro-inflammatory cytokines interleukin6(IL-6) and C-C motif chemokine ligand 2 (CCL2) in LPS group was significantly up-regulated (P<0.01), and the serum creatine level was increased (P<0.01). Compared with LPS group and vehicle group, serum creatine level in GW4064 intervention group was decreased (P<0.05), renal pathological injury was alleviated and the expression of inflammatory factors (IL-6 and CCL2)was down-regulated (P<0.05). At the same time, LPS inhibited FXR expression in protein and mRNA levels in kidney. Also LPS inhibited the expression of FXR in PTECs in vitro (P<0.05). Compared with LPS group and DMSO group, GW4064 intervention group significantly inhibited pro-inflammatory cytokines expression in PTECs (P<0.05). Conclusions LPS inhibits renal FXR expression. Activation of FXR reduces LPS-induced pro-inflammatory cytokines production in PTECs, and alleviates LPS-induce inflammation and AKI. |
| keywords:farnesoid X receptor lipopolysaccharide acute kidney injury inflammation |
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