scholarly journals P0530A NOVEL LNCRNA(LRAN9884) PROMOTES AKI VIA MAINTAINING MINCLE-DEPENDENT M1 MACROPHAGE PHENOTYPE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yingying Zhang ◽  
Chen Yu
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Rt Pcr ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Inflammatory Macrophage

Abstract Background and Aims Macrophages are key inflammatory cells and play a critical role in renal inflammation in acute kidney injury (AKI). M1 inflammatory macrophage and M2 anti-inflammatory macrophage act reverse role. Phenotype of macrophages is highly flexible and can be changed over time. However, the underlying mechanism of M1 and M2 macrophage phenotype switching during AKI is still largely unclear. In our previous study, we identified a novel lncRNA (LRNA9884) might contribute to inflammation according to modifying macrophages. The present study was designed to uncover the pathogenic role and the underlying mechanism of LRNA9884 in cisplatin-induced AKI. Method Expression level and pattern of LRNA9884 were examined in cisplatin-induced AKI mice. The regulatory mechanisms of LRNA9884 was investigated in cultured bone marrow–derived macrophages (BMDMs) in vitro by silencing or overexpressing of LRNA9884. Flow Cytometer, fluorescence in situ hybridization (FISH) and other multiple molecular biological techniques were applied to figure out the role of LRNA9884 under acute kidney injury. Results LRNA9884 was significantly upregulated in the kidney of cisplatin-induced mice and was associated with the progression of the renal inflammation by using RT-PCR and ISH assay. FISH assay with immunofluorescence co-staining detected that LRNA9884 was largely expressed in the nucleus of macrophage in cisplatin-induced mice kidney compared with the sham group at day 1 after AKI injury. LRNA9884 was remarkedly induced by TNF-α (10ng/ml) in BMDMs as time- and dose- dependent. Western blot and RT-PCR showed that silencing of LRNA9884 effectively inhibited upregulated of macrophage-inducible C-type lectin (Mincle) and iNOS induced by TNF-α. More importantly, we identified that LRNA9884 maintained M1 macrophages phenotype by triggering mincle production at transcriptional level as evidenced by ChIP assay. Conclusion LRNA9884 is a mincle-dependent lncRNA that highly-expressed in macrophages under AKI development. Targeting of LRNA9884 effectively blocked the inflammatory response via promoting the transition M1 macrophage to M2 macrophage phenotype. This study will shed new lights on the understanding of pathological role of novel LRNA9884 in AKI.

scholarly journals MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xudong Wang ◽  
Yali Wang ◽  
Mingjian Kong ◽  
Jianping Yang
Keyword(s):  
Acute Kidney Injury ◽  
Inflammatory Response ◽  
Periodic Acid ◽  
Kidney Injury ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Tnf Α

Abstract Background: Septic acute kidney injury is considered as a severe and frequent complication that occurs during sepsis. The present study was performed to understand the role of miR-22-3p and its underlying mechanism in sepsis-induced acute kidney injury. Methods: Rats were injected with adenovirus carrying miR-22-3p or miR-NC in the caudal vein before cecal ligation. Meanwhile, HK-2 cells were transfected with the above adenovirus following LPS stimulation. We measured the markers of renal injury (blood urea nitrogen (BUN), serum creatinine (SCR)). Histological changes in kidney tissues were examined by hematoxylin and eosin (H&E), Masson staining, periodic acid Schiff staining and TUNEL staining. The levels of IL-1β, IL-6, TNF-α and NO were determined by ELISA assay. Using TargetScan prediction and luciferase reporter assay, we predicted and validated the association between PTEN and miR-22-3p. Results: Our data showed that miR-22-3p was significantly down-regulated in a rat model of sepsis-induced acute kidney injury, in vivo and LPS-induced sepsis model in HK-2 cells, in vitro. Overexpression of miR-22-3p remarkably suppressed the inflammatory response and apoptosis via down-regulating HMGB1, p-p65, TLR4 and pro-inflammatory factors (IL-1β, IL-6, TNF-α and NO), both in vivo and in vitro. Moreover, PTEN was identified as a target of miR-22-3p. Furthermore, PTEN knockdown augmented, while overexpression reversed the suppressive role of miR-22-3p in LPS-induced inflammatory response. Conclusions: Our results showed that miR-22-3p induced protective role in sepsis-induced acute kidney injury may rely on the repression of PTEN.

scholarly journals The role of hepatocellular death and systemic inflammation in the development of acute kidney injury in acute decompensation of alcoholic liver cirrhosis

2021 ◽  
pp. 66-71
Author(s):  
A. S. Rodina ◽  
M. E. Shubina ◽  
I. V. Kurbatova ◽  
L. V. Topchieva ◽  
O. P. Dudanova
Keyword(s):  
Acute Kidney Injury ◽  
Systemic Inflammation ◽  
Kidney Injury ◽  
Alcoholic Liver Cirrhosis ◽  
Group I ◽  
Tnf Α ◽  
Acute Decompensation ◽  
Group Ii ◽  
Hepatocellular Death

The aim of the study was to assess the role of hepatocellular death and systemic inflammation in the development of acute kidney injury (AKI) in acute decompensation of alcoholic liver cirrhosis (AD ALC).Materials and methods. 125 patients with ALC were examined: 20 (16.0%) (group I) with signs of hepatorenal syndromeacute kidney injury (HRS-AKI) at the age of 57.13 ± 9,08 years, 13 men (65.0%) and 105 (84.0%) patients (group II) without such a syndrome at the age of 56.30 ± 9.6 years., 62 men (59.0%). Along with liver tests, a markers of hepatocyte apoptosis and cytokines were determined by ELISA: fragments of cytokeratin-18 (FCK-18) ("Biotech" Sweden), cytokines — TNF-α, IL-1β, IL-4, IL-6, IL-8 (“Vector-Best”, Russia). Grade and index of acute on chronic liver failure (ACLF) were determined using an on-line calculator (www.efclif.com/scientific-activity/score-calculators/clif-c-aclf).Results. The hepatocellular death indicators were significantly higher in patients of group I with HRS-AKI compared with patients of group II without HRS-AKI: FCK-18-1609.44 ± 542.79 U / l versus 975.77±607.59 U / l, bilirubin — 242.64 ± 98.14 pmol/l versus 145.09 ± 79.35 pmol/l, inflammation indicators — TNF-α — 9.28 ± 3,11 pg/ml versus 6.59 ± 2.21 pg/ml, IL-6-54.79 ± 17.7 pg/ml versus 36.71 ± 18.05 pg/ml, CRP — 49.68 ± 23.23 mg/l versus 22.07 ± 20.40 mg/l, leukocytes — 12.23 ± 3.28x109/l versus 8,66 ± 2,31x109/l (everywhere p <0.05). ACLF developed in all (100.0%) patients of group I, its grade was 2.73±0.76 and score — 56.33 ± 4.01; ACLF developed only in 37 (35,2%) patients of group II, its grade was1.05±0.24 (p<0,05) and score was 47.45 ± 4,80 (p <0.05).Conclusion. The development of HRS-AKI in patients with acute decompensation of ALC was associated with significantly higher rates of hepatocytic apoptosis, hyperbilirubinemia, systemic inflammation, frequency and severity of ACLF.

Dynamic Role of Macrophage Sub Types for Development of Atherosclerosis and Potential Use of Herbal Immunomodulators as Imminent Therapeutic Strategy

2020 ◽  
Vol 18 ◽  
Author(s):  
Parimalanandhini Duraisamy ◽  
Sangeetha Ravi ◽  
Mahalakshmi Krishnan ◽  
Catherene M. Livya ◽  
Beulaja Manikandan ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Atherosclerotic Lesion ◽  
Foam Cell Formation ◽  
Atherosclerosis Progression ◽  
Proinflammatory Mediators ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Inflammatory Site

: Atherosclerosis, a major contributor to cardiovascular disease is a global alarm causing mortality worldwide. Being a progressive disease in the arteries, it mainly causes recruitment of monocytes to the inflammatory sites and subside pathological conditions. Monocyte-derived macrophage mainly acts in foam cell formation by engorging the LDL molecules, oxidizes it into Ox-LDL and leads to plaque deposit development. Macrophages in general differentiate, proliferate and undergo apoptosis at the inflammatory site. Frequently two subtypes of macrophages M1 and M2 has to act crucially in balancing the micro-environmental conditions of endothelial cells in arteries. The productions of proinflammatory mediators like IL-1, IL-6, TNF-α by M1 macrophage has atherogenic properties majorly produced during the early progression of atherosclerotic plaques. To counteract cytokine productions and M1-M2 balance, secondary metabolites (phytochemicals) from plants act as a therapeutic agent in alleviating atherosclerosis progression. This review summarizes the fundamental role of the macrophage in atherosclerotic lesion formation along with its plasticity characteristic as well as recent therapeutic strategies using herbal components and anti-inflammatory cytokines as potential immunomodulators.

scholarly journals SIRT1 attenuates sepsis-induced acute kidney injury via Beclin1 deacetylation-mediated autophagy activation

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Zhiya Deng ◽  
Maomao Sun ◽  
Jie Wu ◽  
Haihong Fang ◽  
Shumin Cai ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protective Effect ◽  
Cell Model ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
Autophagy Induction ◽  
Promising Therapeutic Approach ◽  
Related Proteins ◽  
Caecal Ligation And Puncture

AbstractOur previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.

scholarly journals Clearance of inflammatory cytokines in patients with septic acute kidney injury during renal replacement therapy using the EMiC2 filter (Clic-AKI study)

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Nuttha Lumlertgul ◽  
Anna Hall ◽  
Luigi Camporota ◽  
Siobhan Crichton ◽  
Marlies Ostermann
Keyword(s):  
Acute Kidney Injury ◽  
Growth Factor ◽  
Replacement Therapy ◽  
Kidney Injury ◽  
Final Analysis ◽  
Adsorptive Capacity ◽  
Clearance Rates ◽  
Plasma Cytokine ◽  
Tnf Α ◽  
Ifn Γ

Abstract Background The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance. Methods This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations. Results Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period. Conclusion EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal. Trial registration: NCT03231748, registered on 27th July 2017.

scholarly journals A zebrafish model of infection-associated acute kidney injury

2018 ◽  
Vol 315 (2) ◽  
pp. F291-F299 ◽  
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.

Acute kidney injury secondary to renal large B-cell lymphoma: role of early renal biopsy

2010 ◽  
Vol 43 (1) ◽  
pp. 237-240 ◽  
Author(s):  
Suhail Al-Salam ◽  
Ahmad Shaaban ◽  
Maha Alketbi ◽  
Naveed U. Haq ◽  
Samra Abouchacra
Keyword(s):  
Acute Kidney Injury ◽  
B Cell ◽  
Renal Biopsy ◽  
Cell Lymphoma ◽  
Kidney Injury ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell
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