CXCL16 regulates cisplatin-induced acute kidney injury

Liu, Hua; Zhang, Zhengmao; He, Liqun; Wang, Yanlin

doi:10.18632/oncotarget.9386

Cited by 31 publications

(27 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, we reported that inflammatory cytokines have an important role in cisplatin-induced AKI. 22,23 Here we found that Nox4 overexpression increased the levels of cisplatin-induced inflammatory cytokines, including TNF-α, IL-1β and IL-6 mRNA levels, compared with the control group (Figure 5e). Thus these data indicate that Nox4 overexpression accelerates cisplatininduced AKI.…”

Section: Resultsmentioning

confidence: 67%

NADPH oxidase 4 promotes cisplatin-induced acute kidney injury via ROS-mediated programmed cell death and inflammation

Meng

Ren

Gao

et al. 2018

Laboratory Investigation

164

117

View full text Add to dashboard Cite

The goal of this study was to elucidate the functional role of Nox4 during acute kidney injury (AKI). NADPH oxidases are a major source of reactive oxygen species (ROS) in the kidney in normal and pathological conditions. Among NADPH oxidase isoforms, NADPH oxidase4 (Nox4) is highly expressed in the kidney and has an important role in kidney diseases, such as diabetic nephropathy and renal carcinoma. We previously found that Nox4 expression significantly increased in the toxic AKI model. However, its functional role and mechanism of action in AKI are still unknown. We scavenged ROS with apocynin in vitro and in vivo and found it attenuated cisplatin-triggered renal function decline. It also alleviated programmed cell death and renal inflammation, indicating a critical role for ROS in mediating AKI. Nox4 protein and mRNA levels were substantially upregulated by cisplatin in vivo and in vitro. Nox4 knockdown alleviated cisplatin-induced cell death and inflammatory response, while Nox4 overexpression aggravated them. Moreover, N-acetyl-L-cysteine (NAC)-mediated inhibition of ROS suppressed cell injury led by Nox4 overexpression, indicating Nox4-mediated ROS generation may be the key mediator in cisplatin-induced nephrotoxicity. Mechanistically, excessive expression of Nox4 induced programmed cell death, especially RIP-mediated necroptosis. Finally, we tested whether Nox4 is a potential therapeutic target using an AKI mouse model by injecting a lentivirus-packaged Nox4 shRNA plasmid through tail vein. Disruption of Nox4 led to renal function recovery, kidney damage relief and reduced inflammation. We conclude that Nox4 aggravates cisplatin-induced nephrotoxicity by promoting ROS-mediated programmed cell death and inflammation. Thus Nox4 may serve as a potential therapeutic target in the treatment of AKI.

show abstract

Section: Resultsmentioning

confidence: 67%

NADPH oxidase 4 promotes cisplatin-induced acute kidney injury via ROS-mediated programmed cell death and inflammation

Meng

Ren

Gao

et al. 2018

Laboratory Investigation

164

117

View full text Add to dashboard Cite

show abstract

“…Substantial evidence has indicated that tubular cell apoptosis contributes to the pathogenesis of AKI, which plays an important role in renal fibrosis [18]. Therefore, we examined the effect of vehicle and TAK1 overexpression transfection treatment on apoptosis of renal tubular epithelial cell with sham or H/R treatment.…”

Section: Upregulation Of Tak1 Aggravates Apoptosis Of Renal Tubular Ementioning

confidence: 99%

TAK1 mediates apoptosis via p38 involve in ischemia-induced renal fibrosis

Zhou

Zhong

Huang

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

Renal fibrosis is a common and characteristic symptom of chronic kidney disease (CKD). However, the molecular mechanisms of renal fibrosis remain elusive. Ischemia injury, as a major cause of AKI, deserves more attention in order to improve the knowledge of AKI-induced fibrosis. Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) interacts directly with TGF-β, which play a critical role in the progression of fibrosis. Therefore, the present study aimed to investigate the role of TAK1 in the pathogenesis of ischemia-induced renal fibrosis. Compared with mice in the vehicle group, mice intraperitoneally injected with TAK1 inhibitor were found to have lower serum creatinine, less tubular damage and more mild fibrosis following ischemia-induced AKI. Furthermore, inhibition of TAK1 reduced p38 phosphorylation, decreased expression of Bax and caspase 3 and apoptosis cells in kidneys of mice treated with IR-induced AKI. Compared with vehicle-treated renal tubular epithelial cells, TAK1 overexpression cells were found to have a higher apoptosis and fibrosis index level and p38 phosphorylation following hypoxia/reoxygenation (H/R) treatment. Furthermore, the p38 inhibitor combined with TAK1 overexpression verified the role of TAK1/p38 signaling pathway in apoptosis and fibrosis index level of renal tubular epithelial cells treated with H/R. Thus, our results show that TAK1 plays an important role in the pathogenesis of ischemia-induced renal fibrosis and may mediate p38-regulated cell apoptosis.

show abstract

“…Increasing evidence has indicated that tubular necrosis/apoptosis is an important mechanism underlying IR-induced AKI [ 17 , 18 ]. Therefore, we investigated tubular epithelial cell apoptosis induced by IR to confirm the success of the model.…”

Section: Resultsmentioning

confidence: 99%

Systematic analysis of the expression profile of non-coding RNAs involved in ischemia/reperfusion-induced acute kidney injury in mice using RNA sequencing

2017

View full text Add to dashboard Cite

Acute kidney injury (AKI) is a common and serious disease characterized by a rapid decline in renal function and has an unacceptably high mortality rate with no effective treatment beyond supportive care. AKI can be induced by many factors such as ischemia/reperfusion (IR), sepsis, and drug-induced nephrotoxicity. However, the molecular mechanisms of AKI are poorly understood. A non-coding RNA (ncRNA) is a RNA molecule that is not translated into a protein. NcRNAs play multiple roles in cellular processes, and mutations or imbalances of these molecules within the body can cause a variety of diseases. Although growing evidence has supported the key role of ncRNAs in AKI, the specific mechanism remains largely unknown. In this study, the second-generation gene sequencing was performed to investigate the expression patterns of ncRNAs, including microRNA (miRNA), long non-coding RNAs, and circular RNAs, in the kidneys of mice subjected to IR-induced AKI. This information will contribute to future research of the mechanism of ncRNAs in the pathogenesis of AKI and facilitate the identification of novel therapeutic targets of ncRNAs.

show abstract

CXCL16 regulates cisplatin-induced acute kidney injury

Cited by 31 publications

References 37 publications

NADPH oxidase 4 promotes cisplatin-induced acute kidney injury via ROS-mediated programmed cell death and inflammation

NADPH oxidase 4 promotes cisplatin-induced acute kidney injury via ROS-mediated programmed cell death and inflammation

TAK1 mediates apoptosis via p38 involve in ischemia-induced renal fibrosis

Systematic analysis of the expression profile of non-coding RNAs involved in ischemia/reperfusion-induced acute kidney injury in mice using RNA sequencing

Contact Info

Product

Resources

About