More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases

Buonafine, Mathieu; Martínez‐Martínez, Ernesto; Jaisser, Frédéric

doi:10.1042/cs20171592

Cited by 114 publications

(127 citation statements)

References 132 publications

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“…However, it was largely preserved by treatment with AMD3100 (Figure F, J, and K). To further confirm the role of CXCR4 in tubular cell injury, we examined the mRNA expression of neutrophil gelatinase–associated lipocalin (NGAL) and transforming growth factor‐β1 (TGF‐β1), two markers of tubular cell injury by quantitative real‐time PCR. As shown in Figure L and M, administration of AMD3100 significantly blocked UUO‐induced up‐regulation of NGAL and TGF‐β1.…”

Section: Resultsmentioning

confidence: 99%

C‐X‐C motif chemokine receptor 4 aggravates renal fibrosis through activating JAK/STAT/GSK3β/β‐catenin pathway

Liu

Feng

Miao

et al. 2020

J Cellular Molecular Medi

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Chronic kidney disease (CKD) has a high prevalence worldwide. Renal fibrosis is the common pathological feature in various types of CKD. However, the underlying mechanisms are not determined. Here, we adopted different CKD mouse models and cultured human proximal tubular cell line to examine the expression of C-X-C motif chemokine receptor 4 (CXCR4) and β-catenin signalling, as well as their relationship in renal fibrosis. In CKD mice and humans with a variety of nephropathies, CXCR4 was dramatically up-regulated in tubules, with a concomitant activation of β-catenin. CXCR4 expression level was positively correlated with the expression of β-catenin target MMP-7. AMD3100, a CXCR4 receptor blocker, and gene knockdown of CXCR4 significantly inhibited the activation of JAK/STAT and β-catenin signalling, protected against tubular injury and renal fibrosis. CXCR4-induced renal fibrosis was inhibited by treatment with ICG-001, an inhibitor of β-catenin signalling. In HKC-8 cells, overexpression of CXCR4 induced activation of β-catenin and deteriorated cell injury. These effects were inhibited by ICG-001. Stromal cell-derived factor (SDF)-1α, the ligand of CXCR4, stimulated the activation of JAK2/STAT3 and JAK3/STAT6 signalling in HKC-8 cells. Overexpression of STAT3 or STAT6 decreased the abundance of GSK3β mRNA. Silencing of STAT3 or STAT6 significantly blocked SDF-1α-induced activation of β-catenin and fibrotic lesions. These results uncover a novel mechanistic linkage between CXCR4 and β-catenin activation in renal fibrosis in association with JAK/STAT/GSK3β pathway. Our studies also suggest that targeted inhibition of CXCR4 may provide better therapeutic effects on renal fibrosis by inhibiting multiple downstream signalling cascades.

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Section: Resultsmentioning

confidence: 99%

C‐X‐C motif chemokine receptor 4 aggravates renal fibrosis through activating JAK/STAT/GSK3β/β‐catenin pathway

Liu

Feng

Miao

et al. 2020

J Cellular Molecular Medi

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“…34 Non-haeme iron trafficking in cells can be regulated by LCN2. 35 Dekens et al 30 found an increase of brain iron deposition in LCN2 deficit mice and also that these mice had a lower learning ability in the training session. This suggests that the existence of LCN2 could be involved in iron regulation and may be involved in cognitive alterations.…”

Section: ↔ Cognitionmentioning

confidence: 99%

“…Iron dysregulation in the brain could also be one of several causes of the impairment of learning and memory . Non‐haeme iron trafficking in cells can be regulated by LCN2 . Dekens et al found an increase of brain iron deposition in LCN2 deficit mice and also that these mice had a lower learning ability in the training session.…”

Section: Lcn2 With Respect To Physiological Condition and Cognitionmentioning

confidence: 99%

Lipocalin‐2: Its perspectives in brain pathology and possible roles in cognition

Pinyopornpanish

Chattipakorn

2019

J Neuroendocrinology

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Lipocalin‐2 (LCN2) has been known to play an important role in pathological conditions, specifically in response to inflammation, infection and injury to cells. Recently, several research teams have been interested in investigating its association with cognition during the progression of pathology. Previous studies have demonstrated that LCN2 is not correlated with cognitive function under normal physiological conditions, although LCN2 has been negatively associated with cognition and some neuropathologies. Increasing LCN2 production is associated with reduced cognitive performance in a rodent model. However, further studies are needed to explore the potential underlying mechanisms of LCN2 on cognitive dysfunction, as well as its clinical relevance. This review aims to summarise the evidence available from in vitro, in vivo and clinical studies concerning the possible role of LCN2 on cognitive function following the onset of pathological conditions. Any contradictory evidence is also assessed and presented.

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“…Here, we analyzed the positive impact of topical pharmacological MR blockade on impaired wound healing of streptozotocin (STZ)-treated mice and of db-db mice, a model of type 2 diabetes. We focused on inflammation and angiogenesis and identified LCN2, a primary MR target (Buonafine et al, 2018;Martínez-Martínez et al, 2017), as a potential mechanism involved in these beneficial effects.…”

Section: Introductionmentioning

confidence: 99%

Cutaneous Wound Healing in Diabetic Mice Is Improved by Topical Mineralocorticoid Receptor Blockade

Nguyen

Farman

Palacios

et al. 2020

Journal of Investigative Dermatology

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Skin ulcers resulting from impaired wound healing are a serious complication of diabetes. Unresolved inflammation, associated with the dysregulation of both the phenotype and function of macrophages, is involved in the poor healing of diabetic wounds. Here, we report that topical pharmacological inhibition of the mineralocorticoid receptor (MR) by canrenoate or MR small interfering RNA can resolve inflammation to improve delayed skin wound healing in diabetic mouse models; importantly, wounds from normal mice are unaffected. The beneficial effect of canrenoate is associated with an increased ratio of anti-inflammatory M2 macrophages to proinflammatory M1 macrophages in diabetic wounds. Furthermore, we show that MR blockade leads to downregulation of the MR target, LCN2, which may facilitate macrophage polarization toward the M2 phenotype and improve impaired angiogenesis in diabetic wounds. Indeed, diabetic LCN2-deficient mice showed improved wound healing associated with macrophage M2 polarization and angiogenesis. In addition, recombinant LCN2 protein prevented IL-4einduced macrophage switch from M1 to M2 phenotype. In conclusion, topical MR blockade accelerates skin wound healing in diabetic mice via LCN2 reduction, M2 macrophage polarization, prevention of inflammation, and induction of angiogenesis.

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More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases

Cited by 114 publications

References 132 publications

C‐X‐C motif chemokine receptor 4 aggravates renal fibrosis through activating JAK/STAT/GSK3β/β‐catenin pathway

C‐X‐C motif chemokine receptor 4 aggravates renal fibrosis through activating JAK/STAT/GSK3β/β‐catenin pathway

Lipocalin‐2: Its perspectives in brain pathology and possible roles in cognition

Cutaneous Wound Healing in Diabetic Mice Is Improved by Topical Mineralocorticoid Receptor Blockade

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