Annexin A1 alleviates kidney injury by promoting the resolution of inflammation in diabetic nephropathy

Wu, Liang; Liu, Changjie; Chang, Dong‐Yuan; Zhan, Rui; Sun, Jing; Cui, Shu; Eddy, Sean; Nair, Viji; Tanner, Emily C.; Brosius, Frank C.; Looker, Helen C.; Nelson, Robert G.; Kretzler, Matthias; Wang, Jiancheng; Xu, Ming; Ju, Wenjun; Zhao, Ming‐Hui; Chen, Min; Zheng, Lemin

doi:10.1016/j.kint.2021.02.025

Cited by 53 publications

(47 citation statements)

References 31 publications

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“…Our previous study found that ANXA1 was upregulated in kidney of patients with diabetic nephropathy and was correlated with renal function and renal outcomes (33). Ka et al (35) demonstrated that urinary levels of ANXA1 were significant higher in secondary glomerular diseases (such as diabetic nephropathy and LN) than in primary glomerular disorders and normal controls.…”

Section: Discussionmentioning

confidence: 95%

“…In addition, ANXA1 shows protective roles in various renal diseases. In mice with diabetic nephropathy, ANXA1 ameliorates kidney injuries through facilitating the resolution of inflammation (33). ANXA1 mimetic peptide (Ac2-26) protects against renal ischemia/reperfusion injury by abortion of neutrophil extravasation and attenuation of macrophage infiltration (34).…”

Section: Discussionmentioning

confidence: 99%

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Renal Expression of Annexin A1 Is Associated With the Severity of Renal Injury in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Chen

et al. 2022

Front. Med.

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BackgroundIncreasing studies demonstrated the importance of activation of neutrophils in the pathogenesis of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Previous studies showed that annexin A1 (ANXA1) inhibited the recruitment, transendothelial migration and respiratory burst of neutrophils and induced apoptosis of neutrophils. The current study aimed to investigate the plasma and renal levels of ANXA1 as well as their association with the disease severity in AAV patients.MethodsThirty-one AAV patients in active stage and 35 AAV patients in remission stage were recruited. The expression of ANXA1 in renal specimens was assessed by immunohistochemistry. The co-localization of ANXA1 with renal intrinsic and infiltrating cells was detected by double immunofluorescence. The plasma levels of ANXA1 were determined by ELISA. The association of plasma and renal levels of ANXA1 with clinicopathological parameters was further analyzed.ResultsPlasma levels of ANXA1 were significantly higher in active AAV patients than those in AAV patients in remission as well as healthy controls. The renal expression of ANXA1 was significantly higher in active AAV patients than in healthy controls and disease controls. Double immunofluorescence assay showed that ANXA1 was expressed in glomerular endothelial cells, mesangial cells, podocytes, proximal tubular epithelial cells, neutrophils, monocytes/macrophages and T cells in AAV patients. The mean optical density of ANXA1 in glomeruli was correlated with serum creatinine levels (r = −0.491, P = 0.005) and eGFR (r = 0.492, P = 0.005) at renal biopsy and the proportion of crescents (r = −0.423, P = 0.018) in renal specimens of AAV patients. The expression of ANXA1 in glomeruli of AAV patients achieving complete renal recovery was significantly higher than those achieving partial renal recovery.ConclusionIn AAV patients, the renal expression of ANXA1 was associated with the severity of renal injury.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Renal Expression of Annexin A1 Is Associated With the Severity of Renal Injury in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Chen

et al. 2022

Front. Med.

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“…With respect to diabetes mellitus, increased renal Annexin A1 is shown to correlate with kidney function and outcomes in established diabetic nephropathy in a human cohort [ 47 ]. According, using the STZ-injected/high fat-fed (STZ/HF) mice, it was shown that Annexin A1 deficiency exacerbated renal injury manifested as exacerbated albuminuria, mesangial matrix expansion, tubulointerstitial lesions, kidney inflammation and fibrosis.…”

Section: Role Of Annexin A1 In Pathologies Of the Kidneymentioning

confidence: 99%

“…Further, treatment with Ac2-26 attenuated kidney injury in db/db mice (a genetic model of type 2 diabetes) and in diabetic Annexin A1 knockout mice. Mechanistic studies revealed that intracellular Annexin A1 binds to the p65 subunit of nuclear factor-κB (NF-κB), thereby inhibiting its activity and reducing inflammation [ 47 ]. Thus, Annexin A1 may serve as a therapeutic option to ameliorate diabetic nephropathy.…”

Section: Role Of Annexin A1 In Pathologies Of the Kidneymentioning

confidence: 99%

Therapeutic Potential of Annexin A1 Modulation in Kidney and Cardiovascular Disorders

Mozaffari

2021

Cells

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Renal and cardiovascular disorders are very prevalent and associated with significant morbidity and mortality. Among diverse pathogenic mechanisms, the dysregulation of immune and inflammatory responses plays an essential role in such disorders. Consequently, the discovery of Annexin A1, as a glucocorticoid-inducible anti-inflammatory protein, has fueled investigation of its role in renal and cardiovascular pathologies. Indeed, with respect to the kidney, its role has been examined in diverse renal pathologies, including acute kidney injury, diabetic nephropathy, immune-mediated nephropathy, drug-induced kidney injury, kidney stone formation, and renal cancer. Regarding the cardiovascular system, major areas of investigation include the role of Annexin A1 in vascular abnormalities, atherosclerosis, and myocardial infarction. Thus, this review briefly describes major structural and functional features of Annexin A1 followed by a review of its role in pathologies of the kidney and the cardiovascular system, as well as the therapeutic potential of its modulation for such disorders.

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“…Finally, administration of Ac2-26, an ANAX1 mimetic, ameliorated renal lipotoxicity in both diabetic ANAX1 knockout mice and diabetic db/db mice. In a recent study, the same group also reported that ANAX1 overexpression ameliorated DN and that ANAX1 expression is upregulated and correlates with kidney function and outcomes from data from a cohort of patients with diabetes (1,2). ANAX1, also known as lipocortin-1 or p35, was originally discovered as a Ca 21 -dependent substrate of the EGF receptor tyrosine kinase.…”

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confidence: 99%

Annexin 1 Mimetic Ac2-26 Holds Promise for the Treatment of Diabetic Nephropathy

Zhang

Harris

2021

Diabetes

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Annexin A1 alleviates kidney injury by promoting the resolution of inflammation in diabetic nephropathy

Cited by 53 publications

References 31 publications

Renal Expression of Annexin A1 Is Associated With the Severity of Renal Injury in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Renal Expression of Annexin A1 Is Associated With the Severity of Renal Injury in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Therapeutic Potential of Annexin A1 Modulation in Kidney and Cardiovascular Disorders

Annexin 1 Mimetic Ac2-26 Holds Promise for the Treatment of Diabetic Nephropathy

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