scholarly journals SP061TRANSIENT INCREASE IN CD39 AMELIORATES ACUTE RENAL INJURY WHEREAS CHRONIC INCREASE IN CD39 EXACERBATES RENAL FIBROSIS AFTER ISCHEMIA REPERFUSION INJURY: EVIDENCE FOR A PROFIBROTIC ACTION OF CHRONICALLY ELEVATED ADENOSINE LEVEL

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii400-iii400
Author(s):  
Veena Roberts ◽  
Bo Lu ◽  
Peter J Cowan ◽  
Karen M Dwyer ◽  
Duncan J Campbell
Keyword(s):  
Reperfusion Injury ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Acute Renal Injury

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 Overexpression of SP1 restores autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Chong Huang ◽  
Yan Chen ◽  
Bin Lai ◽  
Yan-Xia Chen ◽  
Cheng-Yun Xu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Akt Pathway ◽  
Acute Renal Injury ◽  
Injury Model ◽  
Renal Ischemia Reperfusion Injury

Abstract Background Acute kidney injury (AKI) is a major kidney disease with poor clinical outcome. SP1, a well-known transcription factor, plays a critical role in AKI and subsequent kidney repair through the regulation of various cell biologic processes. However, the underlying mechanism of SP1 in these pathological processes remain largely unknown. Methods An in vitro HK-2 cells with anoxia-reoxygenation injury model (In vitro simulated ischemic injury disease) and an in vivo rat renal ischemia-reperfusion injury model were used in this study. The expression levels of SP1, miR-205 and PTEN were detected by RT-qPCR, and the protein expression levels of SP1, p62, PTEN, AKT, p-AKT, LC3II, LC3I and Beclin-1 were assayed by western blot. Cell proliferation was assessed by MTT assay, and the cell apoptosis was detected by flow cytometry. The secretions of IL-6 and TNF-α were detected by ELISA. The targeted relationship between miR-205 and PTEN was confirmed by dual luciferase report assay. The expression and positioning of LC-3 were observed by immunofluorescence staining. TUNEL staining was used to detect cell apoptosis and immunohistochemical analysis was used to evaluate the expression of SP1 in renal tissue after ischemia-reperfusion injury in rats. Results The expression of PTEN was upregulated while SP1 and miR-205 were downregulated in renal ischemia-reperfusion injury. Overexpression of SP1 protected renal tubule cell against injury induced by ischemia-reperfusion via miR-205/PTEN/Akt pathway mediated autophagy. Overexpression of SP1 attenuated renal ischemia-reperfusion injury in rats. Conclusions SP1 overexpression restored autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway.

Abstract 193: Antithrombin Perfluorocarbon Nanoparticles Ameliorate Renal Injury Following Transient Warm Ischemia

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Chandu Vemuri ◽  
Junjie Chen ◽  
Rohun U Palekar ◽  
John S Allen ◽  
Xiaoxia Yang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Renal Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Warm Ischemia ◽  
P Value ◽  
Sprague Dawley ◽  
Histologic Analysis ◽  
Microvascular Thrombosis

Objective: Thrombin mediated microvascular thrombosis plays a crucial role in the pathogenesis of acute renal reperfusion injury following transient ischemia. We hypothesize that anti-thrombin nanoparticles will ameliorate acute renal injury by inhibiting microvascular thrombosis. Methods: Adult, male Sprague Dawley rats were randomized into two groups of 5 to receive tail vein injections of saline or nanoparticles loaded with Phe[D]-Pro-Arg-Chloromethylketone (NP-PPACK). Immediately following injection, all animals underwent operative bilateral renal artery occlusion to create 45 minutes of warm ischemia, followed by restoration of renal blood flow. Blood samples were drawn daily and animals were euthanized on day 1 or 7 for histologic analysis of kidney injury (H&E, TUNEL and thrombin staining). Results: Histologic analysis of renal tissue revealed significant apoptosis, necrosis and thrombin accumulation 1 day after ischemia-reperfusion, confirming acute kidney injury. The peak creatinine (mg/dl) on day 1 was significantly lower in NP-PPACK treated animals (0.57 +/- 0.07 (SEM)) than in saline treated controls (1.40 +/- 0.20 (SEM); p-value <0.01). Furthermore, animals treated with NP-PPACK continued to exhibit less renal dysfunction for 7 days after injury (Figure 1). Conclusion: Histologically confirmed intrarenal thrombosis was detected one day after ischemia-reperfusion injury. Targeted inhibition of thrombin with NP-PPACK prevented a decline in renal function following transient occlusion. Future work will focus on defining the underlying mechanisms of this effect.

NEW MODEL OF COLD ISCHEMIA/REPERFUSION INJURY: CCR1 KNOCKOUT MICE ARE PROTECTED AGAINST RENAL INJURY.

1999 ◽  
Vol 67 (7) ◽  
pp. S247 ◽  
Author(s):  
J Pratschke ◽  
P S Topham ◽  
W Gao ◽  
D Paz ◽  
N L Tilney ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Knockout Mice ◽  
Renal Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cold Ischemia ◽  
New Model

scholarly journals Temporal and sex-dependent gene expression patterns in a renal ischemia-reperfusion injury and recovery pig model

2021 ◽  
Author(s):  
Stéphane Nemours ◽  
Luis Castro ◽  
Didac Ribatallada-Soriano ◽  
Maria Eugenia Semidey ◽  
Miguel Aranda ◽  
...  
Keyword(s):  
Sex Differences ◽  
Reperfusion Injury ◽  
Renal Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Pig Model ◽  
Gene Sets ◽  
Renal Ischemia Reperfusion Injury

ABSTRACTMen are more prone to acute kidney injury (AKI) and chronic kidney disease (CKD), progressing to end-stage renal disease (ESRD) than women. Severity and capacity to regenerate after AKI are important determinants of CKD progression, and of patient morbidity and mortality in the hospital setting. To determine sex differences during injury and recovery we have generated a female and male renal ischemia/reperfusion injury (IRI) pig model, which represents a major cause of AKI. Although no differences were found in blood urea nitrogen (BUN) and serum creatinine (SCr) levels between both sexes, females exhibited higher mononuclear infiltrates at basal and recovery, while males showed more tubular damage at injury. Global transcriptomic analyses of kidney biopsies from our IRI pig model revealed a sexual dimorphism in the temporal regulation of genes and pathways relevant for kidney injury and repair, which was also detected in human samples. Enrichment analysis of gene sets revealed five temporal and four sexual patterns governing renal IRI and recovery. Overall, this study constitutes an extensive characterization of the time and sex differences occurring during renal IRI and recovery at gene expression level and offers a template of translational value for further study of sexual dimorphism in kidney diseases.AUTHOR SUMMARYKidneys’ correct functioning is essential for optimal body homeostasis, being their basic functions blood filtration and excretion of wastes and toxins. Inherited or acquired conditions can cause renal dysfunction requiring renal replacement therapy, which will affect patients’ life quality and survival. A major cause of kidney failure is the renal ischemia/reperfusion injury (IRI), which occurs in many clinical situations like kidney transplantation or aortic aneurysm surgery. Interestingly, men are more susceptible to IRI than women, being women more protected against kidney injury. However, the genetics regulating these sex differences in injury and renal repair remained unknown.Here, we provide a novel porcine model to study renal injury and recovery in both males and females. Using this model, we have identified the gene sets involved in renal injury and recovery processes. Moreover, global genetic analyses allowed us to discover the temporal and sex-dependent patterns that regulate those gene sets and, finally, kidney damage and repair. A relevant finding of our study is that males develop a feminized genetic profile during recovery, which may represent a survival mechanism to diminish the androgenic pro-damage effects on kidney cells. To sum up, our results provide novel sex-dependent targets to prevent renal injury and promote kidney recovery.

Ischemic Postconditioning Inhibits the Renal Fibrosis Induced by Ischemia-reperfusion Injury in Rats

Urology ◽  
2012 ◽  
Vol 80 (2) ◽  
pp. 484.e1-484.e7 ◽  
Author(s):  
Xiaodong Weng ◽  
Hao Shen ◽  
Youlin Kuang ◽  
Xiuhen Liu ◽  
Zhiyuan Chen ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Renal Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Postconditioning
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