Role of AP-1 transcription factor Fosl1 on inflammation and nephroprotection during acute kidney injury.

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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Role of ITK signaling in acute kidney injury in mice: Amelioration of acute kidney injury associated clinical parameters and attenuation of inflammatory transcription factor signaling in CD4+ T cells by ITK inhibition

International Immunopharmacology ◽

10.1016/j.intimp.2021.108028 ◽

2021 ◽

Vol 99 ◽

pp. 108028

Author(s):

Ahmed Nadeem ◽

Sheikh F. Ahmad ◽

Naif O. Al-Harbi ◽

Khalid E. Ibrahim ◽

Wedad Sarawi ◽

...

Keyword(s):

Acute Kidney Injury ◽

T Cells ◽

Transcription Factor ◽

Cd4 T Cells ◽

Kidney Injury ◽

Clinical Parameters ◽

Transcription Factor Signaling

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Acute kidney injury in term infants with asphyxia and the role of ACE, AGT2R1, eNOS genes polymorphisms in its development

SOVREMENNAYA PEDIATRIYA ◽

10.15574/sp.2016.76.109 ◽

2016 ◽

Vol 76 (4) ◽

pp. 109-112

Author(s):

O. Korobka ◽

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Term Infants

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

Cell Death and Disease ◽

10.1038/s41419-021-03865-8 ◽

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.

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The Role of Renal Functional Reserve in Predicting Acute Kidney Injury

Critical Care Clinics ◽

10.1016/j.ccc.2020.11.008 ◽

2021 ◽

Author(s):

Dana Y. Fuhrman

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Functional Reserve ◽

Renal Functional Reserve

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Role of intraoperative oliguria in risk stratification for postoperative acute kidney injury in patients undergoing colorectal surgery with an enhanced recovery protocol: A propensity score matching analysis

PLoS ONE ◽

10.1371/journal.pone.0231447 ◽

2020 ◽

Vol 15 (4) ◽

pp. e0231447 ◽

Cited By ~ 1

Author(s):

Jung-Woo Shim ◽

Kyoung Rim Kim ◽

Yoonju Jung ◽

Jaesik Park ◽

Hyung Mook Lee ◽

...

Keyword(s):

Acute Kidney Injury ◽

Colorectal Surgery ◽

Propensity Score ◽

Risk Stratification ◽

Propensity Score Matching ◽

Enhanced Recovery ◽

Kidney Injury ◽

Propensity Score Matching Analysis ◽

Enhanced Recovery Protocol

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A zebrafish model of infection-associated acute kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00328.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. F291-F299 ◽

Cited By ~ 7

Author(s):

Xiaoyan Wen ◽

Liyan Cui ◽

Seth Morrisroe ◽

Donald Maberry ◽

David Emlet ◽

...

Keyword(s):

Acute Kidney Injury ◽

Unmet Need ◽

Kidney Injury ◽

Edwardsiella Tarda ◽

Adult Zebrafish ◽

Zebrafish Model ◽

Pericardial Edema ◽

Kidney Injury Molecule 1 ◽

Dose Dependent

Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish ( Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for S-AKI research. We introduced Edwardsiella tarda to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune reaction was characterized by increased mRNA expressions of il1b, tnfa, tgfb1a, and cxcl8-l1 ( P < 0.0001, P < 0.001, P < 0.001, and P < 0.01, respectively). Increase of host stress response genes ccnd1 and tp53 was observed at 24 h postinjection ( P < 0.0001 and P < 0.05, respectively). Moderate E. tarda infection induced zebrafish mortality of over 50% in larvae and 20% in adults, accompanied by pericardial edema in larvae and renal dysfunction in both larval and adult zebrafish. Expression of AKI markers insulin-like growth factor-binding protein-7 (IGFBP7), tissue inhibitor of metalloproteinases 2 (TIMP-2), and kidney injury molecule-1 (KIM-1) was found to be significantly increased in the septic animals at the transcription level ( P < 0.01, P < 0.05, and P < 0.05) and in nephric tubules compared with noninfected animals. In conclusion, we established a zebrafish model of S-AKI induced by E. tarda injection, with both larval and adult zebrafish showing nephron injury in the setting of infection.

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