Release of HMGB1 in Podocytes Exacerbates Lipopolysaccharide-Induced Acute Kidney Injury.

Published on Sep 27, 2021in Mediators of Inflammation4.711
· DOI :10.1155/2021/5220226
Zhao Gao (Huda: Hubei University), Li Lu (Huda: Hubei University), Xinghua Chen (WHU: Wuhan University)
Objective. Acute kidney injury (AKI) usually occurs during sepsis. Inflammation factors, such as high-mobility group box 1 (HMGB1), are dramatically upregulated under septic conditions. In our current work, the functions of HMGB1 in AKI were explored. Methods. An AKI model was induced by the lipopolysaccharide (LPS) challenge in C57 mice. Podocytes were challenged by LPS for different durations. Subsequently, podocytes transfected with HMGB1 siRNA were exposed to LPS for 24 h. The expressions of supernatant HMGB1 and cellular active caspase-3 were examined by Western blotting analysis. To explore the effect of HMGB1 on tubular epithelial cells (TECs), HK-2 cells were exposed to HMGB1 at various concentrations for 24 h. Epithelial-mesenchymal transition (EMT) of HK-2 cells was evaluated by Western blotting analysis. Mitochondrial division and apoptosis of HK-2 cells were assessed by MitoTracker Red and Western blotting analysis, respectively. Results. Compared with the sham control group, the expression of HMGB1 was increased in the kidney of AKI mice. Moreover, the expression of supernatant HMGB1 was increased in LPS-challenged podocytes compared with the control group. Knockdown of HMGB1 attenuated LPS-induced podocyte injury. Besides, EMT in TECs was triggered by HMGB1. Mitochondrial damage and apoptosis of HK-2 cells exposed to HMGB1 were markedly elevated compared with the control group. Conclusions. Collectively, HMGB1 release in podocytes was induced by LPS, subsequently leading to exacerbated AKI.
#1Ying WangH-Index: 8
#2Zhiwen Liu (CSU: Central South University)H-Index: 12
Last. Zheng DongH-Index: 81
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Autophagy is a conserved, multistep pathway that degrades and recycles dysfunctional organelles and macromolecules to maintain cellular homeostasis. Mammalian target of rapamycin (mTOR) and adenosine-monophosphate activated-protein kinase (AMPK) are major negative and positive regulators of autophagy, respectively. In cisplatin-induced acute kidney injury (AKI) or nephrotoxicity, autophagy is rapidly induced in renal tubular epithelial cells and acts as a cytoprotective mechanism for cell surviv...
#1Yuxiang Liu (Shanxi Medical University)H-Index: 1
#2Jingai Fang (Shanxi Medical University)H-Index: 1
Acute kidney injury (AKI) is a heterogeneous syndrome characterized by a dramatic increase in serum creatinine. Mild AKI may merely be confined to kidney damage and resolve within days; however, severe AKI commonly involves extrarenal organ dysfunction and is associated with high mortality. There is no specific pharmaceutical treatment currently available that can reverse the course of this disease. Notably, mesenchymal stem cells (MSCs) show great promise for the management of AKI by targeting ...
#1Lina Xu (University of Medicine and Health Sciences)H-Index: 1
#2Guyong Hu (University of Medicine and Health Sciences)H-Index: 1
Last. Dong-Lian Wang (University of Medicine and Health Sciences)H-Index: 2
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Abstract Aims To investigate the effects of paclitaxel on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its related mechanisms. Main methods The sepsis-associated AKI was induced by LPS using HK-2 cells. Then the mRNA and protein expression levels of relevant genes in the serum of sepsis patients and HK-2 cells with LPS-induced AKI were detected by qRT-PCR and western blot analyses before and after paclitaxel treatment, respectively. Subsequently, the cell counting kit-8 (CCK-8)...
#1Xin Huang (Kunming University of Science and Technology)H-Index: 2
#2Xiangping Hou (Kunming University of Science and Technology)H-Index: 1
Last. Jin Ru (Kunming University of Science and Technology)H-Index: 3
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Abstract Introduction The present study aimed to investigate whether miR-129-5p can regulate high-mobility group box protein 1 (HMGB1)-modulated TLRs/NF-kappaB inflammatory pathway that contributed to lipopolysaccharide (LPS)-induced podocyte apoptosis and acute kidney injury (AKI). Material and methods In vitro and in vivo models of sepsis were simulated using LPS-administrated podocytes and mice, respectively. The effects of LPS, mR-129-5p mimics and short hairpin RNA of HMGB1 (sh-HMGB1) on po...
#1Célio Geraldo de Oliveira Gomes (UFMG: Universidade Federal de Minas Gerais)H-Index: 2
#2Marcus V. Andrade (UFMG: Universidade Federal de Minas Gerais)H-Index: 15
Last. Eduardo Garcia Vilela (UFMG: Universidade Federal de Minas Gerais)H-Index: 14
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Background. Acute kidney injury (AKI) affects from 20% to 50% of cirrhotic patients, and the one-month mortality rate is 60%. The main cause of AKI is bacterial infection, which worsens circulatory dysfunction through the release of HMGB1 and IL-6. Objectives. To evaluate HMGB1 and IL-6 as biomarkers of morbidity/mortality. Methods. Prospective, observational study of 25 hospitalised cirrhotic patients with AKI. Clinical and laboratory data were collected at the time of diagnosis of AKI, includi...
#1Yao Wang (WHU: Wuhan University)H-Index: 9
#2Haiyue Zhang (WHU: Wuhan University)H-Index: 7
Last. Zuojiong Gong (WHU: Wuhan University)H-Index: 25
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OBJECTIVE: Acute kidney injury (AKI) is a common complication of acute liver failure (ALF). Pyroptosis is a necrosis type related to inflammation. This study aimed to investigate the role of TNF-α/HMGB1 pathway in pyroptosis during ALF and AKI. METHODS: An ALF and AKI mouse model was generated using LPS/D-Gal, and a TNF-α inhibitor, CC-5013, was used to treat the mice. THP-1 cells were induced to differentiate into M1 macrophages, then challenged with either CC-5013 or an HMGB1 inhibitor, glycyr...
#1Kui JinH-Index: 3
#2Yujie MaH-Index: 1
Last. Hernando Gomez (University of Pittsburgh)H-Index: 26
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The purpose was to determine the role of AMPK activation in the renal metabolic response to sepsis, the development of sepsis-induced acute kidney injury (AKI) and on survival. In a prospective experimental study, 167 10- to 12-week-old C57BL/6 mice underwent cecal ligation and puncture (CLP) and human proximal tubule epithelial cells (TEC; HK2) were exposed to inflammatory mix (IM), a combination of lipopolysaccharide (LPS) and high mobility group box 1 (HMGB1). Renal/TEC metabolic fitness was ...
#1Zhao Gao (WHU: Wuhan University)H-Index: 2
#2Xinghua Chen (WHU: Wuhan University)H-Index: 9
Last. Guohua Ding (WHU: Wuhan University)H-Index: 23
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Acute kidney injury (AKI) is a condition that has a high incidence and death rate. Unfortunately, the kidney may not recover completely after AKI, which then develops to chronic kidney disease (CKD). Therefore, it is necessary to identify potential curative targets to avoid its development to CKD. As an NAD(+) -dependent deacetylase, sirtuin 6 (Sirt6) has been linked to different types of biological processes. In the present work, our group investigated the role of Sirt6 in tubular epithelial ce...
#1Huan YangH-Index: 69
#2Haichao WangH-Index: 88
Last. Ulf Andersson (Karolinska University Hospital)H-Index: 83
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High mobility group box 1 (HMGB1) is a highly conserved, nuclear protein present in all cell types. It is a multi-facet protein exerting functions both inside and outside of cells. Extracellular HMGB1 has been extensively studied for its prototypical alarmin functions activating innate immunity, after being actively released from cells or passively released upon cell death. TLR4 and RAGE operate as the main HMGB1 receptors. Disulfide HMGB1 activates the TLR4 complex by binding to MD-2. The bindi...
#1Soulixay SenouthaiH-Index: 3
#2Junjie WangH-Index: 3
Last. Yanwu YouH-Index: 3
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Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases as well as being associated with the progression of kidney disease. Activation of the Wnt/β-catenin pathway is associated with the pathogenesis of podocyte dysfunction and can play a role in renal injury. Furthermore, the expression of fractalkine (FKN) induced by lipopolysaccharides (LPS) is also one of crucial inflammation factors closely related to renal tissue damage. The aim of this study is to explore the mech...
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