Extracellular CIRP induces acute kidney injury via endothelial TREM-1

Siskind, Sara; Zhang, Fangming; Wang, Ping

doi:10.3389/fphys.2022.954815

Cited by 6 publications

(4 citation statements)

References 58 publications

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“…In the multivariate analysis, elevated levels of CIRP were identified as an independent risk factor for AKI. The mice experiment conducted by Siskind et al confirmed that CIRP can induce acute kidney injury by activating renal TREM-1 ( 26 , 27 ). Moreover, a prospective observational study conducted by Xia et al demonstrated that post-CPB levels of CIRP are associated with an increased risk of pulmonary dysfunction.…”

Section: Discussionmentioning

confidence: 96%

Serum CIRP increases the risk of acute kidney injury after cardiac surgery

Feng,

Cao,

Zhao

et al. 2024

Front. Med.

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IntroductionAcute kidney injury (AKI) is a frequent perioperative complication. The underlying mechanisms of cardiac surgery-associated AKI are still not completely elucidated. Cold-induced RNA-binding protein (CIRP) has been subsequently found to be regulated by various stress conditions. During cardiac surgery and cardiopulmonary bypass (CPB), the host is subjected to hypothermia and inadequate organ perfusion, resulting in an upregulation of CIRP secretion. The aim of this study is to evaluate the role of elevated extracellular CIRP level as a contributing factor in the development of AKI.MethodsA total of 292 patients who underwent cardiac surgery were retrospectively enrolled and their serum samples were collected preoperative and postoperative. Demographic data, intraoperative data, in-hospital outcomes, and the occurrence of AKI were also collected for the patients. The correlation between CIRP and intraoperative procedures, as well as its association with postoperative outcomes were analyzed.ResultsIn multivariable analysis, higher ΔCIRP (p = 0.036) and body mass index (p = 0.015) were independent risk factors for postoperative AKI. Meanwhile, patients with postoperative AKI exhibited lower survival rate in 2-year follow-up (p = 0.008). Compared to off-pump coronary artery bypass grafting surgery, patients who underwent on-pump coronary artery bypass grafting, valve surgery, aortic dissection and other surgery showed higher ΔCIRP, measuring 1,093, 666, 914 and 258 pg/mL, respectively (p < 0.001). The levels of ΔCIRP were significantly higher in patients who underwent CPB compared to those who did not (793.0 ± 648.7 vs. 149.5 ± 289.1 pg/mL, p < 0.001). Correlation analysis revealed a positive correlation between ΔCIRP levels and the duration of CPB (r = 0.502, p < 0.001). Patients with higher CIRP levels are at greater risk of postoperative AKI (OR: 1.67, p = 0.032), especially the stage 2–3 AKI (OR: 2.11, p = 0.037).ConclusionCIRP secretion increases with prolonged CPB time after cardiac surgery, and CIRP secretion is positively correlated with the duration of CPB. Cardiac surgeries with CPB exhibited significantly higher levels of CIRP compared to non-CPB surgeries. Elevation of CIRP level is an independent risk factor for the incidence of AKI, especially the severe AKI, and were associated with adverse in-hospital outcomes.

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Section: Discussionmentioning

confidence: 96%

Serum CIRP increases the risk of acute kidney injury after cardiac surgery

Feng,

Cao,

Zhao

et al. 2024

Front. Med.

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“…Upregulation of TREM-1 expression on monocytes and neutrophils by lipopolysaccharide (LPS), bacteria, and fungi has been demonstrated in vitro ( 17 ). Furthermore, increased expression of TREM-1 has been observed in sterile conditions such as autoimmune diseases ( 10 , 11 ), ischemia-reperfusion injury ( 18 ), myocardial infarction ( 19 ), and acute kidney injury ( 20 ). In these studies, the mechanisms of increased TREM-1 expression remained unclear.…”

Section: Discussionmentioning

confidence: 99%

“…However, neutrophils as well as other immune and non-immune cells also express TREM-1 to some extent. Inhibition of TREM-1 expressed on renal endothelial cells reduces the production of inflammatory cytokines and angiogenic factors after stimulation with DAMPs, potentially attenuating acute kidney injury ( 20 ). Furthermore, knockdown of TREM-1 on cardiomyocytes attenuates cardiomyocytes pyroptosis after LPS stimulation ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Radiation upregulates macrophage TREM-1 expression to exacerbate injury in mice

Yamaga

Murao

et al. 2023

Front. Immunol.

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IntroductionExposure to high-dose ionizing radiation causes tissue injury, infections and even death due to immune dysfunction. The triggering receptor expressed on myeloid cells-1 (TREM-1) has been demonstrated to critically amplify and dysregulate immune responses. However, the role of TREM-1 in radiation injury remains unknown. Extracellular cold-inducible RNA-binding protein (eCIRP), a new damage-associated molecular pattern, is released from activated or stressed cells during inflammation. We hypothesized that ionizing radiation upregulates TREM-1 expression via eCIRP release to worsen survivalMethodsRAW264.7 cells and peritoneal macrophages collected from C57BL/6 wild-type (WT) mice were exposed to 5- and 10-Gray (Gy) radiation. C57BL/6 WT and CIRP-/- mice underwent 10-Gy total body irradiation (TBI). TREM-1 expression on RAW264.7 cells and peritoneal macrophages in vitro and in vivo were evaluated by flow cytometry. eCIRP levels in cell culture supernatants and in peritoneal lavage isolated from irradiated mice were evaluated by Western blotting. We also evaluated 30-day survival in C57BL/6 WT, CIRP-/- and TREM-1-/- mice after 6.5-Gy TBI.ResultsThe surface protein and mRNA levels of TREM-1 in RAW264.7 cells were significantly increased at 24 h after 5- and 10-Gy radiation exposure. TREM-1 expression on peritoneal macrophages was significantly increased after radiation exposure in vitro and in vivo. eCIRP levels were significantly increased after radiation exposure in cell culture supernatants of peritoneal macrophages in vitro and in peritoneal lavage in vivo. Moreover, CIRP-/- mice exhibited increased survival after 6.5-Gy TBI compared to WT mice. Interestingly, TREM-1 expression on peritoneal macrophages in CIRP-/- mice was significantly decreased compared to that in WT mice at 24 h after 10-Gy TBI. Furthermore, 30-day survival in TREM-1-/- mice was significantly increased to 64% compared to 20% in WT mice after 6.5-Gy TBI.ConclusionOur data indicate that ionizing radiation increases TREM-1 expression in macrophages via the release of eCIRP, and TREM-1 contributes to worse survival after total body irradiation. Thus, targeting TREM-1 could have the potential to be developed as a novel medical countermeasure for radiation injury.

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“…[ 92 ] In contrast, in eCIRP-induced mouse AKI, the mRNA expression of kidney injury molecule 1 (KIM-1) and NGAL in the kidneys of TREM-1 –/– mice was reduced. [ 93 ] In terms of mechanism, Pan et al [ 94 ] treated HK-2 cell lines in vitro with LPS. They found that TREM-1 promoted apoptosis and inhibited autophagy in HK-2 cells probably through the regulation of the NF-κB pathway.…”

Section: Role Of Trem-1 In Kidney-related Diseasesmentioning

confidence: 99%

Role of triggering receptor expressed on myeloid cells-1 in kidney diseases: A biomarker and potential therapeutic target

Fan,

Xu,

Huo

et al. 2024

Chinese Medical Journal

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Triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily. As an amplifier of the inflammatory response, TREM-1 is mainly involved in the production of inflammatory mediators and the regulation of cell survival. TREM-1 has been studied in infectious diseases and more recently in non-infectious disorders. More and more studies have shown that TREM-1 plays an important pathogenic role in kidney diseases. There is evidence that TREM-1 can not only be used as a biomarker for diagnosis of disease but also as a potential therapeutic target to guide the development of novel therapeutic agents for kidney disease. This review summarized molecular biology of TREM-1 and its signaling pathways as well as immune response in the progress of acute kidney injury, renal fibrosis, diabetic nephropathy, immune nephropathy, and renal cell carcinoma.

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Extracellular CIRP induces acute kidney injury via endothelial TREM-1

Cited by 6 publications

References 58 publications

Serum CIRP increases the risk of acute kidney injury after cardiac surgery

Serum CIRP increases the risk of acute kidney injury after cardiac surgery

Radiation upregulates macrophage TREM-1 expression to exacerbate injury in mice

Role of triggering receptor expressed on myeloid cells-1 in kidney diseases: A biomarker and potential therapeutic target

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