Neutralization of the extracellular HMGB1 released by ischaemic-damaged renal cells protects against renal ischaemia-reperfusion injury

Li, Junhua; Gong, Quan; Zhong, Sen; Wang, Lu; Guo, Hui; Xiang, Ying; Ichim, Tomas E; Wang, Cong-Yi; Chen, Shi; Gong, Feili; Chen, Gang

doi:10.1093/ndt/gfq466

Cited by 90 publications

(96 citation statements)

References 30 publications

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“…We also determined the contribution of the most investigated endogenous RAGE ligand HMGB1 in renal I/R. In line with previous findings [30,31] , we showed that blocking HMGB1 reduces renal I/R-induced injury by dampening the inflammatory response. As we do not see a similar phenotype in RAGE KO mice, the effect of HMGB1 in renal I/R injury cannot be explained by RAGE signaling.…”

Section: Discussionsupporting

confidence: 85%

“…HMGB1 can, however, also induce activation of intracellular signaling pathways via interaction with PRRs other than RAGE including: Toll-like receptor (TLR) 2, TLR-4 and inflammasome NACHT, LRR and PYD domains-containing protein 3 (Nlrp3) [32,33] . We and others have shown that ␣ HMGB1-treated WT mice, TLR2 KO, TLR4 KO and Nlrp3 KO mice display a similar phenotype following renal I/R [16,17,21,30,31,[34][35][36] . Together, these reports implicate that the deleterious effect of HMGB1 in the development of renal I/R injury is not mediated by RAGE signaling, but rather by TLRs and/or Nlrp3.…”

Section: Discussionmentioning

confidence: 71%

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RAGE Does Not Contribute to Renal Injury and Damage upon Ischemia/Reperfusion-Induced Injury

Dessing¹,

Pulskens²,

Teske³

et al. 2011

J Innate Immun

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 71%

RAGE Does Not Contribute to Renal Injury and Damage upon Ischemia/Reperfusion-Induced Injury

Dessing¹,

Pulskens²,

Teske³

et al. 2011

J Innate Immun

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“…56,57 In a model of IRI, neutralizing antibodies against HMGB1 offered significant protection against renal injury, as was concluded based on the reduction in tubular cell apoptosis, blunted elevation of serum creatinine, BUN, TNF-a expression, and pathologic manifestations of injury. 58 However, it should be kept in mind that HMGB1 is also involved in regenerative processes, as judged from the observations that HMGB1 induces both migration and proliferation of vascular-associated stem cells. 24,59 Release of HMGB1 has been reported after IRI.…”

Section: Systemic Inflammation: Three Waves Of Danger Signalingmentioning

confidence: 99%

Messengers without Borders

Ratliff

Rabadi

Vasko

et al. 2013

Journal of the American Society of Nephrology

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The list of signals sent by an injured organ to systemic circulation, so-called danger signals, is growing to include multiple metabolites and secreted moieties, thus revealing a highly complex and integrated network of interlinked systemic proinflammatory and proregenerative messages. Emerging new data indicate that, apart from the well established local inflammatory response to AKI, danger signaling unleashes a cascade of precisely timed, interdependent, and intensity-gradated mediators responsible for development of the systemic inflammatory response. This fledgling realization of the importance of the systemic inflammatory response to the localized injury and inflammation is at the core of this brief overview. It has a potential to explain the additive effects of concomitant diseases or preexisting chronic conditions that can prime the systemic inflammatory response and exacerbate it out of proportion to the actual degree of acute kidney damage. Although therapies for ameliorating AKI per se remain limited, a potentially powerful strategy that could reap significant benefits in the future is to modulate the intensity of danger signals and consequently the systemic inflammatory response, while preserving its intrinsic proregenerative stimuli.

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“…In this context, HMGB1 triggers cellular signaling by binding to TLR4, which activates NFkB through a MyD88-dependent pathway and initiates the inflammatory response by releasing pro-inflammatory cytokines and chemokines 27 . Moreover, HMGB1 directly induces prothrombin expression on endothelial cells, which can contribute to the inflammatory response and exacerbate any renal impairment 12 .…”

Section: Discussionmentioning

confidence: 99%

“…The depletion of ATP subsequently leads to cellular edema, increased osmotic pressure, and cellular decompartementilization 9,10 , which induces high mobility group box 1 (HMGB1) to generate a danger signal through toll-like receptors 2 and 4 11 . This signal strongly promotes the production of inflammatory cytokines, which increase renal stress and stimulate resident macrophages that can destroy renal tissue 12 .…”

Section: Introductionmentioning

confidence: 99%

Strong renal expression of heat shock protein 70, high mobility group box 1, inducible nitric oxide synthase, and nitrotyrosine in mice model of severe malaria

Fitri

Rosmarwati

Rizky

et al. 2017

Rev. Soc. Bras. Med. Trop.

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Introduction:Renal damage is a consequence of severe malaria, and is generally caused by sequestration of Plasmodium falciparum-infected erythrocytes in the renal microcirculation, which leads to obstruction, hypoxia, and ischemia. This triggers high mobility group box 1 (HMGB1) to send a danger signal through toll-like receptors 2 and 4. This signal up-regulates inducible nitric oxide (iNOS) and nitrotyrosine to re-perfuse the tissue, and also increases heat shock protein 70 (HSP70) expression. As no study has examined the involvement of intracellular secondary molecules in this setting, the present study compared the renal expressions of HSP70, HMGB1, iNOS, and nitrotyrosine between mice suffered from severe malaria and normal mice. Methods: C57BL/6 mice were divided into an infected group (intraperitoneal injection of 10 6 P. berghei ANKA) and a noninfected group. Renal damage was evaluated using hematoxylin eosin staining, and immunohistochemistry was used to evaluate the expressions of HSP70, HMGB1, iNOS, and nitrotyrosine. Results: Significant inter-group differences were observed in the renal expressions of HSP70, HMGB1, and iNOS (p=0.000, Mann-Whitney test), as well as nitrotyrosine (p=0.000, independent t test). The expressions of HSP70 and HMGB1 were strongly correlated (p=0.000, R=1.000). No correlations were observed between iNOS and HMGB, HMGB1 and nitrotyrosine, HSP70 and nitrotyrosine, or iNOS and nitrotyrosine. Conclusions: It appears that HMGB1, HSP70, iNOS, and nitrotyrosine play roles in the renal damage that is observed in mice with severe malaria. Only HSP70 expression is strongly correlated with the expression of HMGB1.

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Neutralization of the extracellular HMGB1 released by ischaemic-damaged renal cells protects against renal ischaemia-reperfusion injury

Abstract: These data suggest that released HMGB1 by ischaemic renal parenchyma cells may act as an essential early mediator in delayed inflammatory response during IRI, and targeting HMGB1 may represent a potential approach in the prevention of clinical IRI associated with kidney transplantation.

Cited by 90 publications

References 30 publications

RAGE Does Not Contribute to Renal Injury and Damage upon Ischemia/Reperfusion-Induced Injury

RAGE Does Not Contribute to Renal Injury and Damage upon Ischemia/Reperfusion-Induced Injury

Messengers without Borders

Strong renal expression of heat shock protein 70, high mobility group box 1, inducible nitric oxide synthase, and nitrotyrosine in mice model of severe malaria

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