Annexin A1 tripeptide mimetic increases sirtuin-3 to augment mitochondrial function and limit ischemic kidney injury

Suliman, Hagir B.; Ma, Qing; Zhang, Zhiquan; Ren, Jiafa; Morris, Benjamin T.; Crowley, Steven D.; Ulloa, Luis; Privratsky, Jamie R.

doi:10.1101/2020.12.11.421859

Cited by 5 publications

(5 citation statements)

References 54 publications

(65 reference statements)

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“…Previous studies demonstrated that oxidative stress evoked by TBI boosts neuroin ammation and contributes to neuronal degeneration and cell death in the brain after injury. AnxA1 has not only been con rmed to exert neurological bene t, but also has been demonstrated to correlate with oxidative stress in several disease conditions, including a chronic obstructive pulmonary disease in vitro model induced by cigarette smoke extract (Yu and Zhang, 2022) and ischemic kidney injury (Suliman et al, 2021). Thus we set out to investigate the effect of AnxA1 on expression of oxidative stress factors in DAI.…”

Section: Annexin A1 De Ciency Signi Cantly Increased the Apoptotic In...mentioning

confidence: 99%

“…In addition, AnxA1 peptide Ac2-26 signi cantly suppressed the activity of NADPH oxidase and malondialdehyde to decrease oxidative stress, lung injury and epithelium apoptosis in acute respiratory distress syndrome rats (Ju et al, 2023). Besides, in the kidney following ischemic injury, AnxA1 limited ROS production and increased antioxidant enzymes to abrogate oxidative stress and attenuate tubular cell death, which nally preserves the kidney against the ischemia (Suliman et al, 2021). Furthermore, Ac2-26 signi cantly ameliorated neuronal apoptosis, reduced the volume of cerebral infarct and improved the neurological function of mice on cerebral I/R (ischemic/reperfusion) injury (Xu et al, 2021).…”

Section: Introductionmentioning

confidence: 98%

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Annexin A1 conveys neuroprotective function via inhibiting oxidative stress in diffuse axonal injury of rats

Zheng,

Li,

et al. 2024

NeuroReport

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Diffuse axonal injury (DAI) is a critical pathological facet of traumatic brain injury (TBI). Oxidative stress plays a significant role in the progress of DAI. Annexin A1 (AnxA1) has been demonstrated to benefit from recovery of neurofunctional outcomes after TBI. However, whether AnxA1 exhibits neuronal protective function by modulating oxidative stress in DAI remains unknown. Expression of AnxA1 was evaluated via real-time PCR and western blotting in rat brainstem after DAI. The neurological effect of AnxA1 following DAI through quantification of modified neurologic severity score (mNSS) was compared between wild-type and AnxA1-knockout rats. Brain edema and neuronal apoptosis, as well as expression of oxidative factors and inflammatory cytokines, were analyzed between wild-type and AnxA1 deficiency rats after DAI. Furthermore, mNSS, oxidative and inflammatory cytokines were assayed after timely administration of recombinant AnxA1 for DAI rats. In the brainstem of DAI, the expression of AnxA1 remarkably increased. Ablation of AnxA1 increased the mNSS score and brain water content of rats after DAI. Neuron apoptosis in the brainstem after DAI was exaggerated by AnxA1 deficiency. In addition, AnxA1 deficiency significantly upregulated the level of oxidative and inflammatory factors in the brainstem of DAI rats. Moreover, mNSS decreased by AnxA1 treatment in rats following DAI. Expression of oxidative and inflammatory molecules in rat brainstem subjected to DAI inhibited by AnxA1 administration. AnxA1 exhibited neuronal protective function in the progression of DAI mainly dependent on suppressing oxidative stress and inflammation.

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Section: Annexin A1 De Ciency Signi Cantly Increased the Apoptotic In...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Annexin A1 conveys neuroprotective function via inhibiting oxidative stress in diffuse axonal injury of rats

Zheng,

Li,

et al. 2024

NeuroReport

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“…Ischemia reperfusion model. Ischemia-reperfusion was performed as previously described via unilateral vascular clamping and contralateral nephrectomy (Suliman et al, 2021). Briefly, mice were anesthetized with ketamine/xylazine.…”

Section: Animal Experimentsmentioning

confidence: 99%

Novel anti-inflammatory effects of the IL-1 receptor in kidney myeloid cells following ischemic AKI

Chen,

Lu,

Whitney

et al. 2024

Front. Mol. Biosci.

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Introduction: Acute kidney injury (AKI) is one of the most common causes of organ failure in critically ill patients. Following AKI, the canonical pro-inflammatory cytokine interleukin-1β (IL-1β) is released predominantly from activated myeloid cells and binds to the interleukin-1 receptor R1 (IL-1R1) on leukocytes and kidney parenchymal cells. IL-1R1 on kidney tubular cells is known to amplify the immune response and exacerbate AKI. However, the specific role of IL-1R1 on myeloid cells during AKI is poorly understood. The objective of the present study was to elucidate the function of myeloid cell IL-1R1 during AKI. As IL-1R1 is known to signal through the pro-inflammatory Toll-like receptor (TLR)/MyD88 pathway, we hypothesized that myeloid cells expressing IL-1R1 would exacerbate AKI.Methods: IL-1R1 was selectively depleted in CD11c+-expressing myeloid cells with CD11cCre+/IL-1R1fl/fl (Myel KO) mice. Myel KO and littermate controls (CD11cCre-/IL-1R1fl/fl–Myel WT) were subjected to kidney ischemia/reperfusion (I/R) injury. Kidney injury was assessed by blood urea nitrogen (BUN), serum creatinine and injury marker neutrophil gelatinase-associated lipocalin (NGAL) protein expression. Renal tubular cells (RTC) were co-cultured with CD11c+ bone marrow-derived dendritic cells (BMDC) from Myel KO and Myel WT mice.Results: Surprisingly, compared to Myel WT mice, Myel KO mice displayed exaggerated I/R-induced kidney injury, as measured by elevated levels of serum creatinine and BUN, and kidney NGAL protein expression. In support of these findings, in vitro co-culture studies showed that RTC co-cultured with Myel KO BMDC (in the presence of IL-1β) exhibited higher mRNA levels of the kidney injury marker NGAL than those co-cultured with Myel WT BMDC. In addition, we observed that IL-1R1 on Myel WT BMDC preferentially augmented the expression of anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra/Il1rn), effects that were largely abrogated in Myel KO BMDC. Furthermore, recombinant IL-1Ra could rescue IL-1β-induced tubular cell injury.Discussion: Our findings suggest a novel function of IL-1R1 is to serve as a critical negative feedback regulator of IL-1 signaling in CD11c+ myeloid cells to dampen inflammation to limit AKI. Our results lend further support for cell-specific, as opposed to global, targeting of immunomodulatory agents.

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“…Renoprotective effects of AnxA1 have been demonstrated for a variety of not primarily immune-mediated conditions including diabetic nephropathy (Wu et al, 2021), ischemia/ reperfusion injury (Facio et al, 2011;Suliman et al, 2021) and calcineurin inhibitor toxicity (Araujo et al, 2010;Araujo et al, 2012). Protective mechanisms include antiinflammatory and antifibrotic effects via formyl peptide receptor 2 signaling, alteration of MAP kinase signaling and inhibition of TGF-β and NF-kB (Neymeyer et al, 2015;Purvis et al, 2018;Wu et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Annexin A1 exerts renoprotective effects in experimental crescentic glomerulonephritis

et al. 2022

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Non-resolving inflammation plays a critical role during the transition from renal injury towards end-stage renal disease. The glucocorticoid-inducible protein annexin A1 has been shown to function as key regulator in the resolution phase of inflammation, but its role in immune-mediated crescentic glomerulonephritis has not been studied so far.Methods: Acute crescentic glomerulonephritis was induced in annexin A1-deficient and wildtype mice using a sheep serum against rat glomerular basement membrane constituents. Animals were sacrificed at d5 and d10 after nephritis induction. Renal leukocyte abundance was studied by immunofluorescence and flow cytometry. Alterations in gene expression were determined by RNA-Seq and gene ontology analysis. Renal levels of eicosanoids and related lipid products were measured using lipid mass spectrometry.Results: Histological analysis revealed an increased number of sclerotic glomeruli and aggravated tubulointerstitial damage in the kidneys of annexin A1-deficient mice compared to the wildtype controls. Flow cytometry analysis confirmed an increased number of CD45+ leukocytes and neutrophil granulocytes in the absence of annexin A1. Lipid mass spectrometry showed elevated levels of prostaglandins PGE2 and PGD2 and reduced levels of antiinflammatory epoxydocosapentaenoic acid regioisomers. RNA-Seq with subsequent gene ontology analysis revealed induction of gene products related to leukocyte activation and chemotaxis as well as regulation of cytokine production and secretion.Conclusion: Intrinsic annexin A1 reduces proinflammatory signals and infiltration of neutrophil granulocytes and thereby protects the kidney during crescentic glomerulonephritis. The annexin A1 signaling cascade may therefore provide novel targets for the treatment of inflammatory kidney disease.

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Annexin A1 tripeptide mimetic increases sirtuin-3 to augment mitochondrial function and limit ischemic kidney injury

Cited by 5 publications

References 54 publications

Annexin A1 conveys neuroprotective function via inhibiting oxidative stress in diffuse axonal injury of rats

Annexin A1 conveys neuroprotective function via inhibiting oxidative stress in diffuse axonal injury of rats

Novel anti-inflammatory effects of the IL-1 receptor in kidney myeloid cells following ischemic AKI

Annexin A1 exerts renoprotective effects in experimental crescentic glomerulonephritis

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