scholarly journals P0689LINACLOTIDE, THE GUANYLATE CYCLASE C AGONIST LIMITS CARDIAC FIBROSIS FORMATION IN MICE WITH CHRONIC KIDNEY DISEASE AFTER ISCHEMIA-REPERFUSION INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Naohito Isoyama ◽  
Yuki Nakayama ◽  
Kimihiko Nakamura ◽  
Toshiya Hiroyoshi ◽  
Kouki Fujikawa ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Reperfusion Injury ◽  
Western Blotting ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Chronic Phase ◽  
Kidney Injury ◽  
Expression Level

Abstract Background and Aims Cardiovascular disease (CVD) is a major cause of mortality in patients with chronic kidney disease (CKD). Renal ischemia-reperfusion injury (IRI) is a clinically significant condition that progress to CKD after acute kidney injury (AKI). We have reported that the suppression of Trimethylamine-N-oxide (TMAO), a hepatic metabolic product of trimethylamine generated from dietary phosphatidylcholine, by linaclotide could prevent renal fibrosis and improve renal function in the chronic phase after renal IRI. TMAO has been linked directly with progression of CVD too. We investigated whether the reduction of TMAO by linaclotide limits cardiac fibrosis in mouse model of CKD after IRI. Method Linaclotide (100μg/kg) was administered for 2weeks before IRI and continued for 2weeks after IRI. After 2weeks since IRI, removed hearts sections were performed Azan stain to evaluate the level of fibrosis and western blotting to evaluate the expression level of fibronectin. Results The administration of linaclotide significantly improved cardiac fibrosis area (Fig1). Additionally, western blotting showed linaclotide suppress the expression level of fibronectin (Fig2). Conclusion The reduction of TMAO by linaclotide could prevent cardiac fibrosis in the chronic phase after renal IRI. Linaclotide may be a powerful tool for prevention of the cardiorenal syndrome after renal IRI.

scholarly journals New mouse model of chronic kidney disease transitioned from ischemic acute kidney injury

2019 ◽  
Vol 317 (2) ◽  
pp. F286-F295 ◽  
Author(s):  
Jin Wei ◽  
Jie Zhang ◽  
Lei Wang ◽  
Shan Jiang ◽  
Liying Fu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Reperfusion Injury ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury

Acute kidney injury (AKI) significantly increases the risk of development of chronic kidney disease (CKD), which is closely associated with the severity of AKI. However, the underlying mechanisms for the AKI to CKD transition remain unclear. Several animal models with AKI to CKD transition have been generated and widely used in research; however, none of them exhibit the typical changes in glomerular filtration rate or plasma creatinine, the hallmarks of CKD. In the present study, we developed a novel model with a typical phenotype of AKI to CKD transition in C57BL/6 mice. In this model, life-threatening ischemia-reperfusion injury was performed in one kidney, whereas the contralateral kidney was kept intact to maintain animal survival; then, after 2 wk of recovery, when the renal function of the injured kidney restored above the survival threshold, the contralateral intact kidney was removed. Animals of this two-stage unilateral ischemia-reperfusion injury model with pedicle clamping of 21 and 24 min exhibited an incomplete recovery from AKI and subsequent progression of CKD with characteristics of a progressive decline in glomerular filtration rate, increase in plasma creatinine, worsening of proteinuria, and deleterious histopathological changes, including interstitial fibrosis and glomerulosclerosis. In conclusion, a new model of the AKI to CKD transition was generated in C57BL/6 mice.

scholarly journals NLRP3 associated with chronic kidney disease progression after ischemia/reperfusion-induced acute kidney injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhihuang Zheng ◽  
Kexin Xu ◽  
Chuanlei Li ◽  
Chenyang Qi ◽  
Yili Fang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Immune Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Chronic Phase ◽  
Kidney Injury ◽  
Receptor Protein ◽  
Tubular Damage

AbstractNod-like receptor protein 3 (NLRP3), as an inflammatory regulator, has been implicated in acute kidney injury (AKI). Failed recovery after AKI can lead to chronic kidney disease (CKD). However, the role of NLRP3 in the AKI-CKD transition is still unknown. A mild or severe AKI mouse model was performed by using ischemia-reperfusion injury (IRI). We evaluated the renal NLRP3 expression in acute and chronic phases of ischemic AKI, respectively. Although serum creatinine (Cr) and blood urea nitrogen (BUN) levels in AKI chronic phase were equivalent to normal baseline, histological analysis and fibrotic markers revealed that severe AKI-induced maladaptive tubular repair with immune cell infiltration and fibrosis. Tubular damage was restored completely in mild AKI rather than in severe AKI. Of note, persistent overexpression of NLRP3 was also found in severe AKI but not in mild AKI. In the severe AKI-induced chronic phase, there was a long-term high level of NLRP3 in serum or urine. Overt NLRP3 was mainly distributed in the abnormal tubules surrounded by inflammatory infiltrates and fibrosis, which indicated the maladaptive repair. Renal Nlrp3 overexpression was correlated with infiltrating macrophages and fibrosis. Renal NLRP3 signaling-associated genes were upregulated after severe AKI by RNA-sequencing. Furthermore, NLRP3 was found increased in renal tubular epitheliums from CKD biopsies. Together, persistent NLRP3 overexpression was associated with chronic pathological changes following AKI, which might be a new biomarker for evaluating the possibility of AKI-CKD transition.

scholarly journals Chronic Kidney Disease Exacerbates Myocardial Ischemia Reperfusion Injury

Shock ◽  
2018 ◽  
Vol 49 (6) ◽  
pp. 712-720 ◽  
Author(s):  
Junjie Guo ◽  
Jianbing Zhu ◽  
Leilei Ma ◽  
Hongtao Shi ◽  
Jiachang Hu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

scholarly journals RAAS Activation Aggravates Ischemia Reperfusion Injury and Accelerates Progression to Chronic Kidney Disease

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Robert Greite ◽  
Rongjun Chen ◽  
Bita Baniassad ◽  
Song Rong ◽  
Anja Thorenz ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

scholarly journals Huaier Extract Attenuates Acute Kidney Injury to Chronic Kidney Disease Transition by Inhibiting Endoplasmic Reticulum Stress and Apoptosis via miR-1271 Upregulation

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jing-Ying Zhao ◽  
Yu-Bin Wu
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Endoplasmic Reticulum ◽  
Kidney Disease ◽  
Endoplasmic Reticulum Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury

Endoplasmic reticulum stress (ERS) is strongly associated with acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Huaier extract (HE) protects against kidney injury; albeit, the underlying mechanism is unknown. We hypothesized that HE reduces kidney injury by inhibiting ERS. In this study, using an AKI-CKD mouse model of ischemia-reperfusion injury (IRI), we evaluated the effect of HE on AKI-CKD transition. We also explored the underlying molecular mechanisms in this animal model and in the HK-2 human kidney cell line. The results showed that HE treatment improved the renal function, demonstrated by a significant decrease in serum creatinine levels after IRI. HE appreciably reduced the degree of kidney injury and fibrosis and restored the expression of the microRNA miR-1271 after IRI. Furthermore, HE reduced the expression of ERS markers glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and inhibited apoptosis in the IRI group. This in vivo effect was supported by in vitro results in which HE inhibited apoptosis and decreased the expression of CHOP and GRP78 induced by ERS. We demonstrated that CHOP is a target of miR-1271. In conclusion, HE reduces kidney injury, probably by inhibiting apoptosis and decreasing the expression of GRP78 and CHOP via miR-1271 upregulation.

The Long Noncoding RNA-H19 Mediates the Progression of Fibrosis from Acute Kidney Injury to Chronic Kidney Disease by Regulating the miR-196a/Wnt/β-Catenin Signaling

Nephron ◽  
2021 ◽  
pp. 1-11
Author(s):  
Xiangnan Dong ◽  
Rui Cao ◽  
Qiang Li ◽  
Lianghong Yin
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Noncoding Rna ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Collagen I ◽  
Luciferase Reporter ◽  
Kidney Fibrosis

<b><i>Introduction:</i></b> Long noncoding RNAs (lncRNAs) have been reported to be involved in the occurrence and development of various diseases. This study was to investigate the role of lncRNA-H19 in the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) and its underlying mechanism. <b><i>Methods:</i></b> Bilateral renal pedicle ischemia-reperfusion injury (IRI) was used to establish the IRI-AKI model in C57BL/6 mice. The expression levels of lncRNA-H19, miR-196a-5p, α-SMA, collagen I, Wnt1, and β-catenin in mouse kidney tissues and fibroblasts were determined by quantitative real-time PCR and Western blotting. The degree of renal fibrosis was evaluated by hematoxylin and eosin staining. The interaction between lncRNA-H19 and miR-196a-5p was verified by bioinformatics analysis and luciferase reporter assay. Immunohistochemistry and immunofluorescence were used to evaluate the expression of α-SMA and collagen I in kidney tissues and fibroblasts of mice. <b><i>Results:</i></b> lncRNA-H19 is upregulated, and miR-196a-5p is downregulated in kidney tissues of IRI mice. Moreover, miR-196a-5p is a direct target of lncRNA-H19. lncRNA-H19 overexpression promotes kidney fibrosis and activates fibroblasts during AKI-CKD development, while miR-196a-5p overexpression reversed these effects in vitro. Furthermore, lncRNA-H19 overexpression significantly upregulates Wnt1 and β-catenin expression in kidney tissues and fibroblasts of IRI mice, while miR-196a-5p overexpression downregulates Wnt1 and β-catenin expression in kidney tissues and fibroblasts of IRI mice. <b><i>Conclusion:</i></b> lncRNA-H19 induces kidney fibrosis during AKI-CKD by regulating the miR-196a-5p/Wnt/β-catenin signaling pathway.

scholarly journals Cardiac function and tolerance to ischemia–reperfusion injury in chronic kidney disease

2013 ◽  
Vol 29 (8) ◽  
pp. 1514-1524 ◽  
Author(s):  
James M. Kuczmarski ◽  
Christopher R. Martens ◽  
Shannon L. Lennon-Edwards ◽  
David G. Edwards
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Function ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

scholarly journals Mechanisms of Fasting-Mediated Protection against Renal Injury and Fibrosis Development after Ischemic Acute Kidney Injury

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 404 ◽  
Author(s):  
Pedro Rojas-Morales ◽  
Edilia Tapia ◽  
Juan Carlos León-Contreras ◽  
Susana González-Reyes ◽  
Angélica Saraí Jiménez-Osorio ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Reperfusion Injury ◽  
Renal Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Chronic Phase ◽  
Kidney Injury ◽  
Redox Status ◽  
Extracellular Signal

Ischemia-reperfusion injury of the kidney may lead to renal fibrosis through a combination of several mechanisms. We recently demonstrated that fasting protects the rat kidney against oxidative stress and mitochondrial dysfunction in early acute kidney injury, and also against fibrosis development. Here we show that preoperative fasting preserves redox status and mitochondrial homeostasis at the chronic phase of damage after severe ischemia. Also, the protective effect of fasting coincides with the suppression of inflammation and endoplasmic reticulum stress, as well as the down-regulation of the mechanistic target of rapamycin (mTOR) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways in the fibrotic kidney. Our results demonstrate that fasting targets multiple pathophysiological mechanisms to prevent renal fibrosis and damage that results after renal ischemia-reperfusion injury.

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