Lipocalin-2: a novel link between the injured kidney and the bone.
Journal
Current opinion in nephrology and hypertension
ISSN: 1473-6543
Titre abrégé: Curr Opin Nephrol Hypertens
Pays: England
ID NLM: 9303753
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
entrez:
21
6
2022
pubmed:
22
6
2022
medline:
24
6
2022
Statut:
ppublish
Résumé
Fibroblast growth factor 23 (FGF23) excess is associated with left ventricular hypertrophy (LVH) and early mortality in patients with chronic kidney disease (CKD) and in animal models. Elevated Lipocalin-2 (LCN2), produced by the injured kidneys, contributes to CKD progression and might aggravate cardiovascular outcomes. The current review aims to highlight the role of LCN2 in CKD, particularly its interactions with FGF23. Inflammation, disordered iron homeostasis and altered metabolic activity are common complications of CKD, and are associated with elevated levels of kidney-produced LCN2 and bone-secreted FGF23. A recent study shows that elevated LCN2 increases FGF23 production, and contributes to cardiac injury in patients and animals with CKD, whereas LCN2 reduction in mice with CKD reduces FGF23, improves cardiovascular outcomes and prolongs lifespan. In this manuscript, we discuss the potential pathophysiological functions of LCN2 as a major kidney-bone crosstalk molecule, linking the progressive decline in kidney function to excessive bone FGF23 production. We also review associations of LCN2 with kidney, cardiovascular and bone and mineral alterations. We conclude that the presented data support the design of novel therapeutic approaches to improve outcomes in CKD.
Identifiants
pubmed: 35727169
doi: 10.1097/MNH.0000000000000804
pii: 00041552-202207000-00004
pmc: PMC9219284
mid: NIHMS1801236
doi:
Substances chimiques
Lipocalin-2
0
Fibroblast Growth Factors
62031-54-3
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
312-319Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK102815
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114158
Pays : United States
Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Références
Lv JC, Zhang LX. Prevalence and disease burden of chronic kidney disease. Adv Exp Med Biol 2019; 1165:3–15.
Saran R, Robinson B, Abbott KC, et al. US Renal Data System 2019 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis 2020; 75: (1 Suppl 1): A6–A7.
Honeycutt AA, Segel JE, Zhuo X, et al. Medical costs of CKD in the Medicare population. J Am Soc Nephrol 2013; 24:1478–1483.
Carney EF. The impact of chronic kidney disease on global health. Nat Rev Nephrol 2020; 16:251.
Collaboration GBDCKD. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2020; 395:709–733.
Herzog CA, Asinger RW, Berger AK, et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2011; 80:572–586.
Remuzzi G, Benigni A, Remuzzi A. Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. J Clin Invest 2006; 116:288–296.
Isakova T, Wahl P, Vargas GS, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 2011; 79:1370–1378.
Stubbs JR, He N, Idiculla A, et al. Longitudinal evaluation of FGF23 changes and mineral metabolism abnormalities in a mouse model of chronic kidney disease. J Bone Mineral Res 2012; 27:38–46.
Wolf M. Forging forward with 10 burning questions on FGF23 in kidney disease. J Am Soc Nephrol 2010; 21:1427–1435.
Gutierrez O, Isakova T, Rhee E, et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005; 16:2205–2215.
Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM. Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 2011; 109:697–711.
Shiizaki K, Tsubouchi A, Miura Y, et al. Calcium phosphate microcrystals in the renal tubular fluid accelerate chronic kidney disease progression. J Clin Invest 2021; 131:e145693.
Scialla JJ, Astor BC, Isakova T, et al. Mineral metabolites and CKD progression in African Americans. J Am Soc Nephrol 2013; 24:125–135.
Schwarz S, Trivedi BK, Kalantar-Zadeh K, Kovesdy CP. Association of disorders in mineral metabolism with progression of chronic kidney disease. Clin J Am Soc Nephrol 2006; 1:825–831.
Liu S, Tang W, Zhou J, et al. Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol 2006; 17:1305–1315.
Kurosu H, Ogawa Y, Miyoshi M, et al. Regulation of fibroblast growth factor-23 signaling by klotho. J Biol Chem 2006; 281:6120–6123.
Urakawa I, Yamazaki Y, Shimada T, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 2006; 444:770–774.
Bai X, Miao D, Li J, et al. Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders. Endocrinology 2004; 145:5269–5279.
Larsson T, Marsell R, Schipani E, et al. Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis. Endocrinology 2004; 145:3087–3094.
Shimada T, Mizutani S, Muto T, et al. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 2001; 98:6500–6505.
Shimada T, Yamazaki Y, Takahashi M, et al. Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism. Am J Physiol Renal Physiol 2005; 289:F1088-95.
Titan SM, Zatz R, Graciolli FG, et al. FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol 2011; 6:241–247.
Kendrick J, Cheung AK, Kaufman JS, et al. FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol 2011; 22:1913–1922.
Hsu HJ, Wu MS. Fibroblast growth factor 23: a possible cause of left ventricular hypertrophy in hemodialysis patients. Am J Med Sci 2009; 337:116–122.
Fliser D, Kollerits B, Neyer U, et al. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol 2007; 18:2600–2608.
Gutierrez OM, Mannstadt M, Isakova T, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. New Engl J Med 2008; 359:584–592.
Ali FN, Hassinger A, Price H, Langman CB. Preoperative plasma FGF23 levels predict acute kidney injury in children: results of a pilot study. Pediatr Nephrol 2013; 28:959–962.
Arnlov J, Carlsson AC, Sundstrom J, et al. Serum FGF23 and risk of cardiovascular events in relation to mineral metabolism and cardiovascular pathology. Clin J Am Soc Nephrol 2013; 8:781–786.
Baia LC, Humalda JK, Vervloet MG, et al. Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation. Clin J Am Soc Nephrol 2013; 8:1968–1978.
Isakova T, Houston J, Santacruz L, et al. Associations between fibroblast growth factor 23 and cardiac characteristics in pediatric heart failure. Pediatr Nephrol 2013; 28:2035–2042.
Kovesdy CP, Quarles LD. The role of fibroblast growth factor-23 in cardiorenal syndrome. Nephron Clin Pract 2013; 123:194–201.
Mirza MA, Larsson A, Lind L, Larsson TE. Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 2009; 205:385–390.
Montford JR, Chonchol M, Cheung AK, et al. Low body mass index and dyslipidemia in dialysis patients linked to elevated plasma fibroblast growth factor 23. Am J Nephrol 2013; 37:183–190.
Nakano C, Hamano T, Fujii N, et al. Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis. Bone 2012; 50:1266–1274.
Prie D, Forand A, Francoz C, et al. Plasma fibroblast growth factor 23 concentration is increased and predicts mortality in patients on the liver-transplant waiting list. PloS One 2013; 8:e66182.
Sugimoto H, Ogawa T, Iwabuchi Y, et al. Relationship between serum fibroblast growth factor-23 level and mortality in chronic hemodialysis patients. Int Urol Nephrol 2014; 46:99–106.
Touchberry CD, Green TM, Tchikrizov V, et al. FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy. Am J Physiol Endocrinol Metab 2013; 304:E863–E873.
Westerberg PA, Tivesten A, Karlsson MK, et al. Fibroblast growth factor 23, mineral metabolism and mortality among elderly men (Swedish MrOs). BMC Nephrol 2013; 14:85.
Wolf M, Molnar MZ, Amaral AP, et al. Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality. J Am Soc Nephrol 2011; 22:956–966.
Faul C, Amaral AP, Oskouei B, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest 2011; 121:4393–4408.
Gutierrez OM, Januzzi JL, Isakova T, et al. Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 2009; 119:2545–2552.
Scialla JJ, Xie H, Rahman M, et al. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol 2014; 25:349–360.
Chang YH, Wu CH, Chou NK, et al. High plasma C-terminal FGF-23 levels predict poor outcomes in patients with chronic kidney disease superimposed with acute kidney injury. Ther Adv Chronic Dis 2020; 11:2040622320964161.
Paul S, Wong M, Akhabue E, et al. Fibroblast growth factor 23 and incident cardiovascular disease and mortality in middle-aged adults. J Am Heart Assoc 2021; 10:e020196.
Dussold C, Gerber C, White S, et al. DMP1 prevents osteocyte alterations, FGF23 elevation and left ventricular hypertrophy in mice with chronic kidney disease. Bone Res 2019; 7:12.
Francis C, Courbon G, Gerber C, et al. Ferric citrate reduces fibroblast growth factor 23 levels and improves renal and cardiac function in a mouse model of chronic kidney disease. Kidney Int 2019; 96:1346–1358.
Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 2007; 71:31–38.
Courbon G, Francis C, Gerber C, et al. Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease. Bone Res 2021; 9:35.
Leaf DE, Jacob KA, Srivastava A, et al. Fibroblast growth factor 23 levels associate with AKI and death in critical illness. J Am Soc Nephrol 2017; 28:1877–1885.
Rabadi S, Udo I, Leaf DE, et al. Acute blood loss stimulates fibroblast growth factor 23 production. Am J Physiol Renal Physiol 2018; 314:F132–F139.
Vervloet MG, van Ittersum FJ, Buttler RM, et al. Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. Clin J Am Soc Nephrol 2011; 6:383–389.
Takashi Y, Kosako H, Sawatsubashi S, et al. Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation. Proc Natl Acad Sci U S A 2019; 116:11418–11427.
de Oliveira Neves FM, Araujo CB, de Freitas DF, et al. Fibroblast growth factor 23, endothelium biomarkers and acute kidney injury in critically-ill patients. J Transl Med 2019; 17:121.
Rygasiewicz K, Hryszko T, Siemiatkowski A, et al. C-terminal and intact FGF23 in critical illness and their associations with acute kidney injury and in-hospital mortality. Cytokine 2018; 103:15–19.
Egli-Spichtig D, Zhang MYH, Perwad F. Fibroblast growth factor 23 expression is increased in multiple organs in mice with folic acid-induced acute kidney injury. Front Physiol 2018; 9:1494.
Simic P, Kim W, Zhou W, et al. Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney. J Clin Invest 2020; 130:1513–1526.
Alber J, Foller M. Lactic acid induces fibroblast growth factor 23 (FGF23) production in UMR106 osteoblast-like cells. Mol Cell Biochem 2022; 477:363–370.
David V, Martin A, Isakova T, et al. Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int 2016; 89:135–146.
Hanudel MR, Eisenga MF, Rappaport M, et al. Effects of erythropoietin on fibroblast growth factor 23 in mice and humans. Nephrol Dial Transplant 2019; 34:2057–2065.
Noonan ML, Ni P, Agoro R, et al. The HIF-PHI BAY 85-3934 (Molidustat) improves anemia and is associated with reduced levels of circulating FGF23 in a CKD mouse model. J Bone Miner Res 2021; 36:1117–1130.
Zhang Q, Doucet M, Tomlinson RE, et al. The hypoxia-inducible factor-1alpha activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia. Bone Res 2016; 4:16011.
Flower DR. Experimentally determined lipocalin structures. Biochim Biophys Acta 2000; 1482 (1–2):46–56.
Goetz DH, Willie ST, Armen RS, et al. Ligand preference inferred from the structure of neutrophil gelatinase associated lipocalin. Biochemistry 2000; 39:1935–1941.
Xiao X, Yeoh BS, Vijay-Kumar M. Lipocalin 2: an emerging player in iron homeostasis and inflammation. Ann Rev Nutr 2017; 37:103–130.
Meheus LA, Fransen LM, Raymackers JG, et al. Identification by microsequencing of lipopolysaccharide-induced proteins secreted by mouse macrophages. J Immunol 1993; 151:1535–1547.
Kjeldsen L, Johnsen AH, Sengelov H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem 1993; 268:10425–10432.
Yan QW, Yang Q, Mody N, et al. The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes 2007; 56:2533–2540.
Mosialou I, Shikhel S, Liu JM, et al. MC4R-dependent suppression of appetite by bone-derived lipocalin 2. Nature 2017; 543:385–390.
Xu MJ, Feng D, Wu H, et al. Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy: a critical role for IL-6/STAT3. Hepatology 2015; 61:692–702.
Chan YR, Liu JS, Pociask DA, et al. Lipocalin 2 is required for pulmonary host defense against Klebsiella infection. J Immunol 2009; 182:4947–4956.
Jha MK, Lee S, Park DH, et al. Diverse functional roles of lipocalin-2 in the central nervous system. Neurosci Biobehav Rev 2015; 49:135–156.
Lee S, Jha MK, Suk K. Lipocalin-2 in the inflammatory activation of brain astrocytes. Crit Rev Immunol 2015; 35:77–84.
Lee S, Park JY, Lee WH, et al. Lipocalin-2 is an autocrine mediator of reactive astrocytosis. J Neurosci 2009; 29:234–249.
Marques FZ, Prestes PR, Byars SG, et al. Experimental and human evidence for lipocalin-2 (neutrophil gelatinase-associated lipocalin [NGAL]) in the development of cardiac hypertrophy and heart failure. J Am Heart Assoc 2017; 6:e005971.
Parmar T, Parmar VM, Perusek L, et al. Lipocalin 2 plays an important role in regulating inflammation in retinal degeneration. J Immunol 2018; 200:3128–3141.
Watanabe H, Takeo T, Tojo H, et al. Lipocalin 2 binds to membrane phosphatidylethanolamine to induce lipid raft movement in a PKA-dependent manner and modulates sperm maturation. Development 2014; 141:2157–2164.
Lee YC, Liao C Jr, Li PT, et al. Mouse lipocalin as an enhancer of spermatozoa motility. Mol Biol Rep 2003; 30:165–172.
Schmidt-Ott KM, Mori K, Li JY, et al. Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 2007; 18:407–413.
Kanda J, Mori K, Kawabata H, et al. An AKI biomarker lipocalin 2 in the blood derives from the kidney in renal injury but from neutrophils in normal and infected conditions. Clin Exp Nephrol 2015; 19:99–106.
Cabezas F, Lagos J, Cespedes C, et al. Megalin/LRP2 expression is induced by peroxisome proliferator-activated receptor -alpha and -gamma: implications for PPARs’ roles in renal function. PloS One 2011; 6:e16794.
Devireddy LR, Gazin C, Zhu X, Green MR. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 2005; 123:1293–1305.
Hvidberg V, Jacobsen C, Strong RK, et al. The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett 2005; 579:773–777.
Moscowitz AE, Asif H, Lindenmaier LB, et al. The importance of melanocortin receptors and their agonists in pulmonary disease. Front Med 2019; 6:145.
Pacifico F, Pisa L, Mellone S, et al. NGAL promotes recruitment of tumor infiltrating leukocytes. Oncotarget 2018; 9:30761–30772.
El Shahawy MS, Hemida MH, Abdel-Hafez HA, et al. Urinary neutrophil gelatinase-associated lipocalin as a marker for disease activity in lupus nephritis. Scand J Clin Lab Invest 2018; 78:264–268.
Wells JM, Brummer RJ, Derrien M, et al. Homeostasis of the gut barrier and potential biomarkers. Am J Physiol Gastrointest Liver Physiol 2017; 312:G171–G193.
Ghosh S, Stepicheva N, Yazdankhah M, et al. The role of lipocalin-2 in age-related macular degeneration (AMD). Cell Mol Life Sci 2020; 77:835–851.
Shao S, Fang H, Dang E, et al. Neutrophil extracellular traps promote inflammatory responses in psoriasis via activating epidermal TLR4/IL-36R crosstalk. Front Immunol 2019; 10:746.
Flo TH, Smith KD, Sato S, et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 2004; 432:917–921.
Aghsaeifard Z, Alizadeh R, Bagheri N. Association between neutrophil gelatinase-associated lipocalin (NGAL) and iron profile in chronic renal disease. Arch Physiol Biochem 2020; 1–5. doi: 10.1080/13813455.2020.1720742. Epub ahead of print. PMID: 31994917.
doi: 10.1080/13813455.2020.1720742.
Krzemien GJ, Panczyk-Tomaszewska M, Turczyn A, et al. Serum neutrophil gelatinase-associated lipocalin for predicting anemia of inflammation in children with urinary tract infection. Central-Eur J Immunol 2021; 46:456–462.
Xiang D, Wang X, Liu P, et al. Increased NGAL level associated with iron store in chronic kidney disease with anemia. Clin Exp Med 2018; 18:563–568.
Neves J, Haider T, Gassmann M, Muckenthaler MU. Iron homeostasis in the lungs-a balance between health and disease. Pharmaceuticals (Basel, Switzerland) 2019; 12:5.
Srinivasan G, Aitken JD, Zhang B, et al. Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis. J Immunol 2012; 189:1911–1919.
Lim D, Jeong JH, Song J. Lipocalin 2 regulates iron homeostasis, neuroinflammation, and insulin resistance in the brains of patients with dementia: evidence from the current literature. CNS Neurosci Ther 2021; 27:883–894.
Guo H, Foncea R, O’Byrne SM, et al. Lipocalin 2, a regulator of retinoid homeostasis and retinoid-mediated thermogenic activation in adipose tissue. J Biol Chem 2016; 291:11216–11229.
Kamble PG, Pereira MJ, Sidibeh CO, et al. Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue. Mol Cell Endocrinol 2016; 427:124–132.
Duan S, Chen J, Wu L, et al. Assessment of urinary NGAL for differential diagnosis and progression of diabetic kidney disease. J Diabetes Complications 2020; 34:107665.
Challen GA, Martinez G, Davis MJ, et al. Identifying the molecular phenotype of renal progenitor cells. J Am Soc Nephrol 2004; 15:2344–2357.
Gwira JA, Wei F, Ishibe S, et al. Expression of neutrophil gelatinase-associated lipocalin regulates epithelial morphogenesis in vitro. J Biol Chem 2005; 280:7875–7882.
Mishra J, Dent C, Tarabishi R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005; 365:1231–1238.
Mishra J, Ma Q, Prada A, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003; 14:2534–2543.
Qiu S, Chen X, Pang Y, Zhang Z. Lipocalin-2 protects against renal ischemia/reperfusion injury in mice through autophagy activation mediated by HIF1alpha and NF-kappab crosstalk. Biomed Pharmacother 2018; 108:244–253.
Mishra J, Mori K, Ma Q, et al. Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 2004; 15:3073–3082.
Kuo CY, Chiu V, Hsieh PC, et al. Loss of function of von Hippel-Lindau trigger lipocalin 2-dependent inflammatory responses in cultured and primary renal tubular cells. Oxid Med Cell Longev 2021; 2021:5571638.
Berger T, Togawa A, Duncan GS, et al. Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury. Proc Natl Acad Sci U S A 2006; 103:1834–1839.
Mertens C, Kuchler L, Sola A, et al. Macrophage-derived iron-bound lipocalin-2 correlates with renal recovery markers following sepsis-induced kidney damage. Int J Mol Sci 2020; 21:7527.
Bonnard B, Ibarrola J, Lima-Posada I, et al. Neutrophil gelatinase-associated lipocalin from macrophages plays a critical role in renal fibrosis via the CCL5 (Chemokine Ligand 5)-Th2 Cells-IL4 (interleukin 4) pathway. Hypertension 2022; 79:352–364.
Patel ML, Sachan R, Misra R, et al. Prognostic significance of urinary NGAL in chronic kidney disease. Int J Nephrol Renovasc Dis 2015; 8:139–144.
Nickolas TL, Forster CS, Sise ME, et al. NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease. Kidney Int 2012; 82:718–722.
Viau A, El Karoui K, Laouari D, et al. Lipocalin 2 is essential for chronic kidney disease progression in mice and humans. J Clin Invest 2010; 120:4065–4076.
Bonnard B, Martinez-Martinez E, Fernandez-Celis A, et al. Antifibrotic effect of novel neutrophil gelatinase-associated lipocalin inhibitors in cardiac and renal disease models. Sci Rep 2021; 11:2591.
Guo L, Zhu B, Yuan H, Zhao W. Evaluation of serum neutrophil gelatinase-associated lipocalin in older patients with chronic kidney disease. Aging Med (Milton) 2020; 3:32–39.
Gu Z, Huang Y, Yang F, et al. The application of neutrophil gelatin-related lipid delivery protein in evaluation of renal function, nutrition, anemia and inflammation in patients with CKD. Nephrol Therapeut 2021; 17:35–41.
Chase LR, Aurbach GD. The effect of parathyroid hormone on the concentration of adenosine 3’,5’-monophosphate in skeletal tissue in vitro. J Biol Chem 1970; 245:1520–1526.
Lavi-Moshayoff V, Wasserman G, Meir T, et al. PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol 2010; 299: F882-9.
Li D, Li H, Bauer C, et al. Lipocalin-2 variants and their relationship with cardio-renal risk factors. Front Endocrinol 2021; 12:781763.
Kim IY, Kim JH, Kim MJ, et al. Plasma neutrophil gelatinase-associated lipocalin is independently associated with left ventricular hypertrophy and diastolic dysfunction in patients with chronic kidney disease. PloS One 2018; 13:e0205848.
Jang HM, Lee JY, An HS, et al. LCN2 deficiency ameliorates doxorubicin-induced cardiomyopathy in mice. Biochemical and biophysical research communications 2022; 588:8–14.
Gu Y, Geng J, Xu Z, et al. Neutrophil gelatinase-associated lipocalin2 exaggerates cardiomyocyte hypoxia injury by inhibiting integrin beta3 signaling. Med Sci Monit 2019; 25:5426–5434.
Kumfu S, Siri-Angkul N, Chattipakorn SC, Chattipakorn N. Silencing of lipocalin-2 improves cardiomyocyte viability under iron overload conditions via decreasing mitochondrial dysfunction and apoptosis. J Cell Physiol 2021; 236:5108–5120.
Rucci N, Capulli M, Piperni SG, et al. Lipocalin 2: a new mechanoresponding gene regulating bone homeostasis. J Bone Miner Res 2015; 30:357–368.
Capulli M, Ponzetti M, Maurizi A, et al. A complex role for lipocalin 2 in bone metabolism: global ablation in mice induces osteopenia caused by an altered energy metabolism. J Bone Miner Res 2018; 33:1141–1153.
Ponzetti M, Ucci A, Maurizi A, et al. Lipocalin 2 influences bone and muscle phenotype in the MDX mouse model of duchenne muscular dystrophy. Int J Mol Sci 2022; 23:958.
Lim WH, Wong G, Lim EM, et al. Circulating lipocalin 2 levels predict fracture-related hospitalizations in elderly women: a prospective cohort study. J Bone Miner Res 2015; 30:2078–2085.
Yao F, Deng Y, Zhao Y, et al. A targetable LIFR-NF-kappaB-LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis. Nat Commun 2021; 12:7333.
Chaudhary N, Choudhary BS, Shah SG, et al. Lipocalin 2 expression promotes tumor progression and therapy resistance by inhibiting ferroptosis in colorectal cancer. Int J Cancer 2021; 149:1495–1511.
Leng X, Ding T, Lin H, et al. Inhibition of lipocalin 2 impairs breast tumorigenesis and metastasis. Cancer Res 2009; 69:8579–8584.
Guo P, Yang J, Jia D, et al. ICAM-1-targeted, Lcn2 siRNA-encapsulating liposomes are potent antiangiogenic agents for triple negative breast cancer. Theranostics 2016; 6:1–13.
Tarin C, Fernandez-Garcia CE, Burillo E, et al. Lipocalin-2 deficiency or blockade protects against aortic abdominal aneurysm development in mice. Cardiovasc Res 2016; 111:262–273.