The inflammation–lipocalin 2 axis may contribute to the development of chronic kidney disease

Hashikata, Atsushi; Yamashita, Akiko; Suzuki, Shigeki; Nagayasu, Shintaro; Shinjo, Takanori; Taniguchi, Ataru; Fukushima, Mitsuo; Nakai, Yoshikatsu; Nin, Kazuko; Watanabe, Nobuhisa; Asano, Tomohiko; Abiko, Yoshimitsu; Kushiyama, Akifumi; Nagasaka, Shoichiro; Nishimura, Fusanori

doi:10.1093/ndt/gft449

Cited by 15 publications

(11 citation statements)

References 29 publications

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“…Furthermore, previous studies have found an association between high sTNF α ‐R1 levels and diabetic nephropathy . Our results suggest that, independent of other risk factors, micro‐inflammation emerges at a very early stage of RF decline and should be considered as a potential independent risk factor in older adults . Of the inflammatory biomarkers tested, sTNF α ‐R1 and sTNF α ‐R2 were the strongest and most consistent predictors of CKD.…”

Section: Discussionsupporting

confidence: 64%

“…Another study demonstrated that angiotensin‐II infusion in mice introduced a fibroinflammatory response that is followed by kidney tubulointerstitial collagen deposition mediated through the TNF‐R1 signaling pathway and speculated that TNF α ‐R1 triggers collagen deposition . A significant association between lipocalin 2 in mesangial cells and sTNF α ‐R2 levels and impaired kidney function has also been reported . Therefore, similar persistent age‐related chronic inflammation might result in structural modification of glomerular and interstitial components of the kidneys, with resulting decline in RF.…”

Section: Discussionmentioning

confidence: 99%

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Inflammation and Trajectory of Renal Function in Community‐Dwelling Older Adults

Salimi

Shardell

Seliger

et al. 2018

J American Geriatrics Society

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Inflammation and Trajectory of Renal Function in Community‐Dwelling Older Adults

Salimi

Shardell

Seliger

et al. 2018

J American Geriatrics Society

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“…Concerning its role in disease, different conditions have been correlated with increased levels of LCN2. Particularly, studies indicate its altered expression in certain types of cancers (Rodvold et al, 2012), coronary diseases (Iqbal et al, 2013), metabolic syndrome (Jang et al, 2012;Yoo et al, 2014), insulin resistance and type 2 diabetes (Yan et al, 2007), chronic kidney disease (Hashikata et al, 2014), autoimmune diseases (Kamata et al, 2012) and in wound repair (Miao et al, 2014). In the brain, the involvement of LCN2 in autoimmune diseases such as MS (Berard et al, 2012;Marques et al, 2012;Nam et al, 2014) and other neurodegenerative disorders such as AD (Choi et al, 2011;Mesquita et al, 2014;Naude et al, 2012) is also suggested.…”

mentioning

confidence: 99%

From the periphery to the brain: Lipocalin-2, a friend or foe?

Ferreira

Mesquita

Sousa

et al. 2015

Progress in Neurobiology

130

109

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Lipocalin-2 (LCN2) is an acute-phase protein that, by binding to iron-loaded siderophores, acts as a potent bacteriostatic agent in the iron-depletion strategy of the immune system to control pathogens. The recent identification of a mammalian siderophore also suggests a physiological role for LCN2 in iron homeostasis, specifically in iron delivery to cells via a transferrin-independent mechanism. LCN2 participates, as well, in a variety of cellular processes, including cell proliferation, cell differentiation and apoptosis, and has been mostly found up-regulated in various tissues and under inflammatory states, being its expression regulated by several inducers. In the central nervous system less is known about the processes involving LCN2, namely by which cells it is produced/secreted, and its impact on cell proliferation and death, or in neuronal plasticity and behaviour. Importantly, LCN2 recently emerged as a potential clinical biomarker in multiple sclerosis and in ageing-related cognitive decline. Still, there are conflicting views on the role of LCN2 in pathophysiological processes, with some studies pointing to its neurodeleterious effects, while others indicate neuroprotection. Herein, these various perspectives are reviewed and a comprehensive and cohesive view of the general function of LCN2, particularly in the brain, is provided.

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“…In response to inflammation and tissue injury, TNFα directly induces the production of lipocalin-2 from intestinal and renal epithelial cells [ 38 ]. Lipocalin-2 is an inflammatory mediator for intestinal and renal inflammation and is positively correlated with inflammatory disease severity [ 38 , 39 , 40 ]. Serum lipocalin-2 are positively correlated with serum levels of soluble TNFR and negatively correlated with glomerular filtration rate [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Intestinal SIRT1 Deficiency-Related Intestinal Inflammation and Dysbiosis Aggravate TNFα-Mediated Renal Dysfunction in Cirrhotic Ascitic Mice

Chou

Liu

Yang

et al. 2021

IJMS

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In advanced cirrhosis, the TNFα-mediated intestinal inflammation and bacteria dysbiosis are involved in the development of inflammation and vasoconstriction-related renal dysfunction. In colitis and acute kidney injury models, activation of SIRT1 attenuates the TNFα-mediated intestinal and renal abnormalities. This study explores the impacts of intestinal SIRT1 deficiency and TNFα-mediated intestinal abnormalities on the development of cirrhosis-related renal dysfunction. Systemic and renal hemodynamics, intestinal dysbiosis [cirrhosis dysbiosis ratio (CDR) as marker of dysbiosis], and direct renal vasoconstrictive response (renal vascular resistance (RVR) and glomerular filtration rate (GFR)) to cumulative doses of TNFα were measured in bile duct ligated (BDL)-cirrhotic ascitic mice. In SIRT1IEC-KO-BDL-ascitic mice, the worsening of intestinal dysbiosis exacerbates intestinal inflammation/barrier dysfunction, the upregulation of the expressions of intestinal/renal TNFα-related pathogenic signals, higher TNFα-induced increase in RVR, and decrease in GFR in perfused kidney. In intestinal SIRT1 knockout groups, the positive correlations were identified between intestinal SIRT1 activity and CDR. Particularly, the negative correlations were identified between CDR and RVR, with the positive correlation between CDR and GFR. In mice with advanced cirrhosis, the expression of intestinal SIRT1 is involved in the linkage between intestinal dysbiosis and vasoconstriction/hypoperfusion-related renal dysfunction through the crosstalk between intestinal/renal TNFα-related pathogenic inflammatory signals.

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The inflammation–lipocalin 2 axis may contribute to the development of chronic kidney disease

Cited by 15 publications

References 29 publications

Inflammation and Trajectory of Renal Function in Community‐Dwelling Older Adults

Inflammation and Trajectory of Renal Function in Community‐Dwelling Older Adults

From the periphery to the brain: Lipocalin-2, a friend or foe?

Intestinal SIRT1 Deficiency-Related Intestinal Inflammation and Dysbiosis Aggravate TNFα-Mediated Renal Dysfunction in Cirrhotic Ascitic Mice

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