scholarly journals Renal tubular arginase‐2 participates in the formation of the corticomedullary urea gradient and attenuates kidney damage in ischemia‐reperfusion injury in mice

2020 ◽  
Vol 229 (3) ◽  
Author(s):  
Camille Ansermet ◽  
Gabriel Centeno ◽  
Sylviane Lagarrigue ◽  
Svetlana Nikolaeva ◽  
Hikari A. Yoshihara ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Damage ◽  
Renal Tubular

P0516DCR2 PROMOTES RENAL FIBROSIS BY ACCELERATING TUBULAR CELL SENESCENCE AFTER ISCHEMIA REPERFUSION INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jia Chen ◽  
Yani He
Keyword(s):  
Reperfusion Injury ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Senescence ◽  
Tubular Cell ◽  
Renal Tubules ◽  
Senescent Phenotype ◽  
Renal Tubular

Abstract Background and Aims Cell senescence of renal tubular epithelial cells (RTECs), which is involved in renal fibrosis, is a key event in the progression of acute kidney injury (AKI). However, the underlying mechanism remains unclear. This study aims to investigate the role and mechanism of decoy receptor 2 (DcR2) in renal fibrosis and cell senescence of RTECs. Method KSP-creDcR2f/f mouse (Tubular DcR2 KO) and Ischemia-Reperfusion (I/R) Injury models were constructed. The models were divided into moderated (ischemia 20min) and severe (ischemia 35min) injury. The expression of renal DcR2, senescent markers (P16, P21, SA-β-gal) and senescent phenotype (IL-6, TGF-β1) were detected. Furthermore, wild type (WT) mice and KSP-creDcR2f/f mice were used to compare the degree of renal tissue and functional damage and the senescence of renal tubular cells after I/R injury. In vitro, knockdown and overexpression experiments were performed by transfected DcR2 siRNA or overexpressed adenovirus in hypoxia-reoxygenation stimulated mouse primary RTEC. The cell senescence and phenotype markers were further detected. Results The levels of Scr, BUN and urinary DcR2 and renal injury scores were significantly increased in I/R group at the early stage (1d) of renal injury compared with sham group. Renal fibrosis was observed in the later stage (21-42d) in severe injury. DcR2 was mainly expressed in renal tubules, and the percentage of tubular DcR2 was increased after I/R injury. DcR2 was co-expressed with P16 and SA-β-gal, and urinary DcR2 levels were related to senescent makers, suggesting that DcR2 was associated with cell senescence. The renal function and renal injury scores were lower in KSP-creDcR2f/f mice than that of WT after renal reperfusion. And the area of renal fibrosis was significantly decreased in KSP-creDcR2f/f mice compared with WT, indicating DcR2 inhibited renal fibrosis. Furthermore, the expression of senescent phenotype were suppressed in tubular DcR2 KO mice after I/R injury, suggesting that DcR2 could promote the senescence of renal tubule cells. Conclusion DcR2 promotes renal fibrosis by accelerating tubular cell senescence after ischemia-reperfusion Injury, suggesting that DcR2 may be a potential intervention target during the progression of AKI.

scholarly journals Fibrinogen β–derived Bβ15-42 peptide protects against kidney ischemia/ reperfusion injury

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1934-1942 ◽  
Author(s):  
Aparna Krishnamoorthy ◽  
Amrendra Kumar Ajay ◽  
Dana Hoffmann ◽  
Tae-Min Kim ◽  
Victoria Ramirez ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
High Sensitivity ◽  
Kidney Damage ◽  
Therapeutic Interventions ◽  
Mrna Levels ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Injury And Repair

AbstractIschemia/reperfusion (I/R) injury in the kidney is a major cause of acute kidney injury (AKI) in humans and is associated with significantly high mortality. To identify genes that modulate kidney injury and repair, we conducted genome-wide expression analysis in the rat kidneys after I/R and found that the mRNA levels of fibrinogen (Fg)α, Fgβ, and Fgγ chains significantly increase in the kidney and remain elevated throughout the regeneration process. Cellular characterization of Fgα and Fgγ chain immunoreactive proteins shows a predominant expression in renal tubular cells and the localization of immunoreactive Fgβ chain protein is primarily in the renal interstitium in healthy and regenerating kidney. We also show that urinary excretion of Fg is massively increased after kidney damage and is capable of distinguishing human patients with acute or chronic kidney injury (n = 25) from healthy volunteers (n = 25) with high sensitivity and specificity (area under the receiver operating characteristic of 0.98). Furthermore, we demonstrate that Fgβ-derived Bβ15-42 peptide administration protects mice from I/R-induced kidney injury by aiding in epithelial cell proliferation and tissue repair. Given that kidney regeneration is a major determinant of outcome for patients with kidney damage, these results provide new opportunities for the use of Fg in diagnosis, prevention, and therapeutic interventions in kidney disease.

scholarly journals Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

2016 ◽  
Vol 17 (10) ◽  
pp. 1728 ◽  
Author(s):  
Luca Villa ◽  
Roberta Buono ◽  
Mara Ferrandi ◽  
Isabella Molinari ◽  
Fabio Benigni ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Rat Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Damage ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury

SP059HEPARANASE A KEY REGULATOR OF THE CHRONIC PROFIBROTIC KIDNEY DAMAGE FOLLOWING ISCHEMIA/REPERFUSION INJURY

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i365-i365 ◽  
Author(s):  
Valentina Masola ◽  
Simona Granata ◽  
Giovanni Gambrao ◽  
Antonio Lupo ◽  
Gianluigi Zaza
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Damage

scholarly journals HDAC2 targeting stabilizes the CoREST complex in renal tubular cells and protects against renal ischemia/reperfusion injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David D. Aufhauser ◽  
Paul Hernandez ◽  
Seth J. Concors ◽  
Ciaran O’Brien ◽  
Zhonglin Wang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Tubules ◽  
Renal Protection ◽  
Renal Tubular Cells ◽  
Renal Ischemia Reperfusion Injury ◽  
Renal Tubular

AbstractHistone/protein deacetylases (HDAC) 1 and 2 are typically viewed as structurally and functionally similar enzymes present within various co-regulatory complexes. We tested differential effects of these isoforms in renal ischemia reperfusion injury (IRI) using inducible knockout mice and found no significant change in ischemic tolerance with HDAC1 deletion, but mitigation of ischemic injury with HDAC2 deletion. Restriction of HDAC2 deletion to the kidney via transplantation or PAX8-controlled proximal renal tubule-specific Cre resulted in renal IRI protection. Pharmacologic inhibition of HDAC2 increased histone acetylation in the kidney but did not extend renal protection. Protein analysis demonstrated increased HDAC1-associated CoREST protein in HDAC2-/- versus WT cells, suggesting that in the absence of HDAC2, increased CoREST complex occupancy of HDAC1 can stabilize this complex. In vivo administration of a CoREST inhibitor exacerbated renal injury in WT mice and eliminated the benefit of HDAC2 deletion. Gene expression analysis of endothelin showed decreased endothelin levels in HDAC2 deletion. These data demonstrate that contrasting effects of HDAC1 and 2 on CoREST complex stability within renal tubules can affect outcomes of renal IRI and implicate endothelin as a potential downstream mediator.

Sign in / Sign up

Export Citation Format

Share Document