Myeloid cyclooxygenase-2/prostaglandin E2/E-type prostanoid receptor 4 promotes transcription factor MafB-dependent inflammatory resolution in acute kidney injury.

2021 ◽  
Author(s):  
Yu Pan ◽  
Shirong Cao ◽  
Andrew S. Terker ◽  
Jiaqi Tang ◽  
Kensuke Sasaki ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Transcription Factor ◽  
Prostaglandin E2 ◽  
Kidney Injury ◽  
Cyclooxygenase 2 ◽  
Prostanoid Receptor

scholarly journals RIP3 impedes transcription factor EB to suppress autophagic degradation in septic acute kidney injury

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Ruizhao Li ◽  
Xingchen Zhao ◽  
Shu Zhang ◽  
Wei Dong ◽  
Li Zhang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Transcription Factor ◽  
Nuclear Translocation ◽  
Kidney Injury ◽  
Septic Acute Kidney Injury ◽  
Transcription Factor Eb ◽  
Autophagic Degradation ◽  
Lps Treatment

AbstractAutophagy is an important renal-protective mechanism in septic acute kidney injury (AKI). Receptor interacting protein kinase 3 (RIP3) has been implicated in the renal tubular injury and renal dysfunction during septic AKI. Here we investigated the role and mechanism of RIP3 on autophagy in septic AKI. We showed an activation of RIP3, accompanied by an accumulation of the autophagosome marker LC3II and the autophagic substrate p62, in the kidneys of lipopolysaccharide (LPS)-induced septic AKI mice and LPS-treated cultured renal proximal tubular epithelial cells (PTECs). The lysosome inhibitor did not further increase the levels of LCII or p62 in LPS-treated PTECs. Moreover, inhibition of RIP3 attenuated the aberrant accumulation of LC3II and p62 under LPS treatment in vivo and in vitro. By utilizing mCherry-GFP-LC3 autophagy reporter mice in vivo and PTECs overexpression mRFP-GFP-LC3 in vitro, we observed that inhibition of RIP3 restored the formation of autolysosomes and eliminated the accumulated autophagosomes under LPS treatment. These results indicated that RIP3 impaired autophagic degradation, contributing to the accumulation of autophagosomes. Mechanistically, the nuclear translocation of transcription factor EB (TFEB), a master regulator of the lysosome and autophagy pathway, was inhibited in LPS-induced mice and LPS-treated PTECs. Inhibition of RIP3 restored the nuclear translocation of TFEB in vivo and in vitro. Co-immunoprecipitation further showed an interaction of RIP3 and TFEB in LPS-treated PTECs. Also, the expression of LAMP1 and cathepsin B, two potential target genes of TFEB involved in lysosome function, were decreased under LPS treatment in vivo and in vitro, and this decrease was rescued by inhibiting RIP3. Finally, overexpression of TFEB restored the autophagic degradation in LPS-treated PTECs. Together, the present study has identified a pivotal role of RIP3 in suppressing autophagic degradation through impeding the TFEB-lysosome pathway in septic AKI, providing potential therapeutic targets for the prevention and treatment of septic AKI.

scholarly journals Chronic nicotine exposure exacerbates acute renal ischemic injury

2011 ◽  
Vol 301 (1) ◽  
pp. F125-F133 ◽  
Author(s):  
Istvan Arany ◽  
Samira Grifoni ◽  
Jeb S. Clark ◽  
Eva Csongradi ◽  
Christine Maric ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Transcription Factor ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Ischemic Injury ◽  
Renal Diseases ◽  
Healthy Population ◽  
Nicotine Exposure ◽  
Chronic Nicotine

Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury.

scholarly journals Adverse Effects of Oral Nonselective and cyclooxygenase-2-Selective NSAIDs on Hospitalization for Acute Kidney Injury

Medicine ◽  
2016 ◽  
Vol 95 (9) ◽  
pp. e2645 ◽  
Author(s):  
Chia-I. Chou ◽  
Chia-Jen Shih ◽  
Yung-Tai Chen ◽  
Shuo-Ming Ou ◽  
Chih-Yu Yang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Effects ◽  
Kidney Injury ◽  
Cyclooxygenase 2

scholarly journals Role of SIK1 in the transition of acute kidney injury into chronic kidney disease

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinxiu Hu ◽  
Jiao Qiao ◽  
Qun Yu ◽  
Bing Liu ◽  
Junhui Zhen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Kidney Injury ◽  
High Morbidity ◽  
Mesenchymal Transition ◽  
Immunohistochemistry Staining ◽  
Hk2 Cells

Abstract Background Acute kidney injury (AKI), with a high morbidity and mortality, is recognized as a risk factor for chronic kidney disease (CKD). AKI-CKD transition has been regarded as one of the most pressing unmet needs in renal diseases. Recently, studies have showed that salt inducible kinase 1 (SIK1) plays a role in epithelial-mesenchymal transition (EMT) and inflammation, which are the hallmarks of AKI-CKD transition. However, whether SIK1 is involved in AKI-CKD transition and by what mechanism it regulates AKI-CKD transition remains unknown. Methods We firstly detected the expression of SIK1 in kidney tissues of AKI patients and AKI mice by immunohistochemistry staining, and then we established Aristolochic acid (AA)-induced AKI-CKD transition model in C57BL/6 mice and HK2 cells. Subsequently, we performed immunohistochemistry staining, ELISA, real-time PCR, Western blot, immunofluorescence staining and Transwell assay to explore the role and underlying mechanism of SIK1 on AKI-CKD transition. Results The expression of SIK1 was down-regulated in AKI patients, AKI mice, AA-induced AKI-CKD transition mice, and HK2 cells. Functional analysis revealed that overexpression of SIK1 alleviated AA-induced AKI-CKD transition and HK2 cells injury in vivo and in vitro. Mechanistically, we demonstrated that SIK1 mediated AA-induced AKI-CKD transition by regulating WNT/β-catenin signaling, the canonical pathway involved in EMT, inflammation and renal fibrosis. In addition, we discovered that inhibition of WNT/β-catenin pathway and its downstream transcription factor Twist1 ameliorated HK2 cells injury, delaying the progression of AKI-CKD transition. Conclusions Our study demonstrated, for the first time, a protective role of SIK1 in AKI-CKD transition by regulating WNT/β-catenin signaling pathway and its downstream transcription factor Twist1, which will provide novel insights into the prevention and treatment AKI-CKD transition in the future.

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