Adenosine Generation and Signaling during Acute Kidney Injury

Bauerle, Jessica D.; Grenz, Almut; Kim, Jaehwan; Lee, H. Thomas; Eltzschig, Holger K.

doi:10.1681/asn.2009121217

Cited by 122 publications

(136 citation statements)

References 89 publications

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“…Elevating the adenosine level in the heart causes vasodilation and an increase in heart rate (33). Adenosine has been implicated in the initial injury process, because it is a well-known signaling molecule for stress and tissue injury (34)(35)(36). From this study, we observed a gradual increase in the adenosine deaminase transcript level (peaking in the T3R1 group).…”

Section: Discussionmentioning

confidence: 50%

Molecular evidence of stress-induced acute heart injury in a mouse model simulating posttraumatic stress disorder

Cho

Lee

Hammamieh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Posttraumatic stress disorder (PTSD) is a common condition induced by life-threatening stress, such as that experienced by soldiers under battlefield conditions. Other than the commonly recognized behavioral and psychological dysfunction, epidemiological studies have also revealed that PTSD patients have a higher risk of other diseases, such as cardiovascular disorders. Using a PTSD mouse model, we investigated the longitudinal transcriptomic changes in heart tissues after the exposure to stress through intimidation. Our results revealed acute heart injury associated with the traumatic experience, reflecting the underlying biological injury processes of the immune response, extracellular matrix remodeling, epithelial-to-mesenchymal cell transitions, and cell proliferation. Whether this type of injury has any longterm effects on heart function is yet to be determined. The differing responses to stress leading to acute heart injury in different inbred strains of mice also suggest that this response has a genetic as well as an environmental component. Accordingly, the results from this study suggest a molecular basis for the observed higher risk of cardiovascular disorders in PTSD patients, which raises the likelihood of cardiac dysfunction induced by long-term stress exposures.systems biology | transcriptome | microRNA

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Section: Discussionmentioning

confidence: 50%

Molecular evidence of stress-induced acute heart injury in a mouse model simulating posttraumatic stress disorder

Cho

Lee

Hammamieh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…32 Adenosine signals through four receptors, among which adora2a is the major immunoregulatory arm of the adenosine signaling system, and a potent protective molecule in vivo capable of blocking inflammation. 33,34 Although adora2a is located in the kidney, 35,36 the protection afforded by adora2a agonists is an effect on T/NKT cells in ischemic renal injury. 6,8,37 So far, several studies have suggested an important link between HIFs and adenosinerelated molecules.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion Injury

Zhang

Han

Dai

et al. 2016

Journal of the American Society of Nephrology

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Natural killer T (NKT) cells are the major early-acting immune cell type and fundamental immune modulators in ischemia-reperfusion injury (IRI). Because lymphocytes are exposed to various oxygen tensions under pathophysiologic conditions, we hypothesize that hypoxia-inducible factors (HIFs) have roles in NKT cell activation, and thus determine the final outcome of renal IRI. In this study, we used Lck-Cre transgenic mice to specifically disrupt HIF-2a in T/NKT cells and found that HIF-2a knockout led to upregulated Fas ligand expression on peripheral NKT cells, but not on conventional T cells. HIF-2a knockout promoted infiltration of NKT cells into ischemic kidneys and exacerbated IRI, which could be mitigated by in vivo NK1.1 + cell depletion or Fas ligand blockade.Compared with wild-type NKT cells, HIF-2a 2/2 NKT cells adoptively transferred to Rag1-knockout mice elicited more severe renal injury, and these mice were not protected by CGS21680, an adenosine A2A receptor agonist. Mechanistically, hypoxia-induced expression of adenosine A2A receptor in NKT cells and CGS21680-induced cAMP production in thymocytes were HIF-2a-dependent. Hydrogen peroxide-induced Fas ligand expression on thymic wild-type NKT cells was significantly attenuated by CGS21680 treatment, but this effect was lost in HIF-2a 2/2 NKT cells. Finally, CGS21680 and LPS, an inducer of HIF-2a in endothelium, synergistically reduced renal IRI substantially, but this effect was absent in Mx1-Cre-induced global HIF-2a-knockout mice. Taken together, our results reveal a hypoxia/HIF-2a/adenosine A2A receptor axis that restricts NKT cell activation when confronted with oxidative stress and thus protects against renal IRI.

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“…The possible explanations are: 1) Iodixanol, as a new generation of iso-osmolar contrast agent, may be less toxic to the kidney; 2) CIN may only present with transient renal dysfunction without significant histological damages to the normal kidneys in healthy mice. Since adenosine receptor expression is changed during ischemic, hypoxic, and inflammation conditions [8][9][10][11][12][13], the pre-existing kidney diseases may be also required in the development of CIN. Further investigation using db/db and hypertension mice will be carried out in our research lab.…”

Section: Creatinine Assay Results After Iodixanol Administration In Nmentioning

confidence: 99%

“…There are reports indicating that the adenosine receptors' expression is changed during ischemic, hypoxic, and inflammation conditions [8][9][10][11][12][13]. We were curious whether contrast media might alter the adenosine receptors' expression.…”

Section: Introductionmentioning

confidence: 99%

The gene expression of adenosine receptors in the processes of contrast induced nephropathy in mouse kidney

Yao¹,

Zhao²,

Gu³

et al. 2013

WJCD

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Adenosine Generation and Signaling during Acute Kidney Injury

Cited by 122 publications

References 89 publications

Molecular evidence of stress-induced acute heart injury in a mouse model simulating posttraumatic stress disorder

Molecular evidence of stress-induced acute heart injury in a mouse model simulating posttraumatic stress disorder

Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion Injury

The gene expression of adenosine receptors in the processes of contrast induced nephropathy in mouse kidney

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