HMGB1 Turns Renal Tubular Epithelial Cells into Inflammatory Promoters by Interacting with TLR4 During Sepsis

Zheng, Shixiang; Pan, Yangbin; Wang, Cairong; Liu, Yipeng; Shi, Ming; Ding, Guohua

doi:10.1089/jir.2015.0067

Cited by 29 publications

(21 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, to date, little progress has been achieved and the mechanisms inducing AKI during sepsis are still mysterious. In our previous study that aimed to look for the possible mechanisms of SAKI, we found out that the alteration of functional status and structure of TECs was critically related to the occurrence of SAKI [34,35]. These findings are consistent with the conclusions of previous studies focusing on AKI.…”

Section: Discussionsupporting

confidence: 89%

MiR-21-3p Plays a Crucial Role in Metabolism Alteration of Renal Tubular Epithelial Cells during Sepsis Associated Acute Kidney Injury via AKT/CDK2-FOXO1 Pathway

Lin

Liu

Wang

et al. 2019

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Objective. Sepsis and associated acute kidney injury (SAKI) are determined to be closely related to poor prognosis. Because the metabolic alterations of tubular epithelial cells (TECs) are crucial for the occurrence and development of SAKI, we carried out this present study to identify the metabolism changes of TECs during SAKI and relevant mechanisms. Methods. Rat SAKI model and rat tubular epithelial cell line were used in our study. ELISA was used to determine the serum cytokines levels. Protein expressions were examined with Western-Blotting and the transcriptions of RNAs were determined with qRT-PCR. ADP/ATP assay and Oil Red O staining were used to examine the energy and lipid metabolism, respectively. Dual-luciferase reporter assay was carried out to determine the interactions between miRNA and specific proteins. Cell cycle arrest and apoptosis were determined with flow cytometry. Results. Sepsis and AKI were induced 12 h after CLP. Energy and lipid metabolism reduced significantly while FOXO1 levels increased remarkably in TECs during SAKI. The expressions of both AKT and CDK2 and the transcriptions of relevant mRNAs reduced significantly in TECs during SAKI while miR-21-3p expression increased remarkably. Both AKT and CDK2 were determined as the direct targets of miR-21-3p. Furthermore, by in vitro experiments, it was demonstrated that FOXO1 levels were regulated by miR-21-3p in TECs via AKT/CDK2 and AKT/CDK2-FOXO1 pathway was crucial in the regulations of miR-21-3p on lipid metabolism, cell cycle arrest, and apoptosis of TECs. Conclusions. MiR-21-3p mediates metabolism and cell fate alterations of TECs via manipulating AKT/CDK2-FOXO1 pathway, and that is crucial in the regulation of energy metabolism of TECs during SAKI.

show abstract

Section: Discussionsupporting

confidence: 89%

MiR-21-3p Plays a Crucial Role in Metabolism Alteration of Renal Tubular Epithelial Cells during Sepsis Associated Acute Kidney Injury via AKT/CDK2-FOXO1 Pathway

Lin

Liu

Wang

et al. 2019

BioMed Research International

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, HMGB1 accumulates in the renal tissue and can enter the urine. Moreover, the interaction between HMGB1 and TLR-4 converts tubular epithelial cells into inflammatory promoters during sepsis (27). In this study, we confirmed that both typical receptors (i.e., receptor for advanced glycation end product, TLR-2, and TLR-4), and inflammatory cytokines were considerably elevated in CLP mice, further supporting the role of HMGB1-mediated inflammation in sepsis.…”

Section: Discussionsupporting

confidence: 79%

SIRT1-mediated HMGB1 deacetylation suppresses sepsis-associated acute kidney injury

Wei

Gao

Dai

et al. 2019

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Sepsis is the leading cause of death in the intensive care unit and continues to lack effective treatment. It is widely accepted that high-mobility group box 1 (HMGB1) is a key inflammatory mediator in the pathogenesis of sepsis. Moreover, some studies indicate that the functions of HMGB1 depend on its molecular localization and posttranslational modifications. Our previous study confirms that sirtuin 1, silent information regulator 2-related enzyme 1 (SIRT1), a type III deacetylase, can ameliorate sepsis-associated acute kidney injury (SA-AKI). We explored the effect and mechanism of SIRT1 on HMGB1 using a mouse model of cecal ligation and puncture-induced sepsis and LPS-treated human kidney (HK-2) cell line. We found that HMGB1 is elevated in the serum but is gradually reduced in kidney cells in the later stages of septic mice. The acetylation modification of HMGB1 is a key process before its nucleus-to-cytoplasm translocation and extracellular secretion in kidney cells, accelerating the development of SA-AKI. Moreover, SIRT1 can physically interact with HMGB1 at the deacetylated lysine sites K28, K29, and K30, subsequently suppressing downstream inflammatory signaling. Thus the SIRT1-HMGB1 signaling pathway is a crucial mechanism in the development of SA-AKI and presents a novel experimental perspective for future SA-AKI research.

show abstract

“…Duan et al (20) evaluated the HMGB1 levels in the serum of 60 patients with HBV-related ACLF, 30 with chronic hepatitis B and 24 healthy kin-1 and, also, IL-6 (31) . Likewise, HMGB1 can accumulate in the renal tissue and urine, stimulating the production of inflammatory cytokines, including IL-6, through interaction with toll-like receptors 4 (32) . Elevated levels of toll-like receptors 4 are found in the renal tubular cells of cirrhotic patients with AKI, suggesting that these receptors may mediate renal injury in the context of infection or systemic inflammation (33) .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Behavior of Levels of Hmgb1 and Il6 as Predictors of Infection, Acute Kidney Injury and Mortality in Cirrhotic Patients With Variceal Bleeding

Vilela

Pinheiro

Saturnino

et al. 2018

Arq. Gastroenterol.

View full text Add to dashboard Cite

BACKGROUND: Gastroesophageal varices and associated bleeding are a major cause of morbidity and mortality in cirrhotic patients. OBJECTIVE: To evaluate the potential role of the biomarkers HMGB1 (High Mobility Group Box 1) and IL-6 (Interleukin-6) as predictors of infection, acute kidney injury and mortality in these patients. METHODS: It is a prospective, observational study that included 32 cirrhotic patients with variceal bleeding. RESULTS: The subjects’mean age was 52±5 years and 20 (62.5%) were male. The average MELD was 17.53±5 and the average MELD-Na was 20.63±6.06. Thirty patients (93.3%) patients were Child-Pugh class B or C. Infection was present in 9 subjects (28.1%), acute kidney injury was present in 6 (18.1%) and 4 (12.5%) patients died. The median serum levels of HMGB1 were 1487 pg/mL (0.1 to 8593.1) and the median serum level of IL-6 was 62.1 pg/mL (0.1 to 1102.4). The serum levels of HMGB1 and IL-6 were significantly higher in patients who developed infection, acute kidney injury and death (P<0.05). The Spearman’s correlations for HMGB1 and IL-6 were 0.794 and 0.374 for infection, 0.53 and 0.374 for acute kidney injury and 0.467 and 0.404 for death, respectively. CONCLUSION: Serum levels of HMGB1 and IL-6 were higher in patients with the three studied outcomes. HMGB1 serum levels showed a high correlation with infection and a moderate correlation with acute kidney injury and death, while IL-6 showed a moderate correlation with infection and death and a low correlation with acute kidney injury.

show abstract

HMGB1 Turns Renal Tubular Epithelial Cells into Inflammatory Promoters by Interacting with TLR4 During Sepsis

Cited by 29 publications

References 36 publications

MiR-21-3p Plays a Crucial Role in Metabolism Alteration of Renal Tubular Epithelial Cells during Sepsis Associated Acute Kidney Injury via AKT/CDK2-FOXO1 Pathway

MiR-21-3p Plays a Crucial Role in Metabolism Alteration of Renal Tubular Epithelial Cells during Sepsis Associated Acute Kidney Injury via AKT/CDK2-FOXO1 Pathway

SIRT1-mediated HMGB1 deacetylation suppresses sepsis-associated acute kidney injury

Evaluation of the Behavior of Levels of Hmgb1 and Il6 as Predictors of Infection, Acute Kidney Injury and Mortality in Cirrhotic Patients With Variceal Bleeding

Contact Info

Product

Resources

About