scholarly journals 1464: TRANSCRIPTION PROFILING OF SEPTIC ACUTE KIDNEY INJURY IDENTIFIED TIFA-REGULATED PYROPTOSIS

2021 ◽  
Vol 50 (1) ◽  
pp. 734-734
Author(s):  
Yiming Li ◽  
Jing zhang ◽  
Zhiyong Peng
2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Ruizhao Li ◽  
Xingchen Zhao ◽  
Shu Zhang ◽  
Wei Dong ◽  
Li Zhang ◽  
...  

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.


2019 ◽  
Vol 41 (4) ◽  
pp. 462-471 ◽  
Author(s):  
Kellen Hyde Elias Pinheiro ◽  
Franciana Aguiar Azêdo ◽  
Kelsy Catherina Nema Areco ◽  
Sandra Maria Rodrigues Laranja

Abstract Acute kidney injury (AKI) has an incidence rate of 5-6% among intensive care unit (ICU) patients and sepsis is the most frequent etiology. Aims: To assess patients in the ICU that developed AKI, AKI on chronic kidney disease (CKD), and/or sepsis, and identify the risk factors and outcomes of these diseases. Methods: A prospective observational cohort quantitative study that included patients who stayed in the ICU > 48 hours and had not been on dialysis previously was carried out. Results: 302 patients were included and divided into: no sepsis and no AKI (nsnAKI), sepsis alone (S), septic AKI (sAKI), non-septic AKI (nsAKI), septic AKI on CKD (sAKI/CKD), and non-septic AKI on CKD (nsAKI/CKD). It was observed that 94% of the patients developed some degree of AKI. Kidney Disease Improving Global Outcomes (KDIGO) stage 3 was predominant in the septic groups (p = 0.018). Nephrologist follow-up in the non-septic patients was only 23% vs. 54% in the septic groups (p < 0.001). Dialysis was performed in 8% of the non-septic and 37% of the septic groups (p < 0.001). Mechanical ventilation (MV) requirement was higher in the septic groups (p < 0.001). Mortality was 38 and 39% in the sAKI and sAKI/CKD groups vs 16% and 0% in the nsAKI and nsAKI/CKD groups, respectively (p < 0.001). Conclusions: Patients with sAKI and sAKI/CKD had worse prognosis than those with nsAKI and nsAKI/CKD. The nephrologist was not contacted in a large number of AKI cases, except for KDIGO stage 3, which directly influenced mortality rates. The urine output was considerably impaired, ICU stay was longer, use of MV and mortality were higher when kidney injury was combined with sepsis.


Renal Failure ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 794-799
Author(s):  
Pan Ying ◽  
Chenguang Yang ◽  
Xianlong Wu ◽  
Qiqi Cai ◽  
Wenwei Xin

2009 ◽  
Vol 36 (3) ◽  
pp. 385-388 ◽  
Author(s):  
Olivier Joannes-Boyau ◽  
Patrick M. Honoré ◽  
Willem Boer ◽  
Thomas Rose

Shock ◽  
2016 ◽  
Vol 45 (2) ◽  
pp. 133-138 ◽  
Author(s):  
Kengo Mayumi ◽  
Tetsushi Yamashita ◽  
Yoshifumi Hamasaki ◽  
Eisei Noiri ◽  
Masaomi Nangaku ◽  
...  

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