Table 2.

Selected experimental and clinical findings associated with altered LCN2 expression in organ disorders.

Organ	Species	Model/disease	Method	LCN2 expression	Finding	References
Kidney	Mouse/human	Chronic kidney disease/proteinuria	qRT-PCR, WB, IHC	Increased LCN2 expression	Induction of Ca2+-dependent ER stress causes albumin to activate ATF4 expression, which in turn induces LCN2 production leading to increased apoptosis and tubulointerstitial damage	El Karoui et al., 2016
	Mouse	Renal allograft damage following transplantation	ELISA, qRT-PCR	Strong upregulation of LCN2	LCN2 improved morphological and functional damage by reducing apoptosis of tubular epithelial cells and stimulating their proliferation	Ashraf et al., 2016
	Mouse	Antibody-induced glomerulonephritis	IHC, ELISA	LCN2 expression is increased in mice with nephrotoxic nephritis	Renal binding of pathogenic antibodies stimulates LCN2 expression	Pawar et al., 2012
	Human	Acute kidney injury (AKI)	ELISA	Strong upregulation of LCN2 in progressive AKI	Urinary high LCN2 expression indicates risk for progression and death of AKI patients	Belcher et al., 2014
	Human newborns	Acute kidney injury/failure	ELISA, WB	Upregulation of LCN2 in serum and blood	LCN2 is a diagnostic marker for AKI in neonates	Jin et al., 2011
Heart	Human/children	Acute heart failure/worsening renal function	ELISA	High plasma LCN2 concentration	Admission plasma LCN2 level can predict worsening renal function in children hospitalized for acute heart failure	Elsharawy et al., 2016
	Mouse, rat	Heart failure/cardiomyocyte apoptosis	NA	NA	Recombinant LCN2 directly induces cardiomyocyte apoptosis which occurs via a mechanism involving elevated intracellular iron levels	Xu et al., 2012
	Mouse	Hypoxia-induced cardiomyocyte apoptosis	qRT-PCR, WB	Transient overexpression by transfection	Induced up-regulation of miR-138 inhibits the hypoxia-induced cardiomyocyte apoptosis via down-regulating expression of pro-apoptotic LCN2; LCN2 is a direct target of miR-138	Xiong et al., 2016
Brain	Human	Mild cognitive impairment (MCI) and Alzheimer's disease (AD)	ELISA	LCN2 levels significantly higher in MCI patients compared to the healthy control	Increased plasma LCN2 levels during MCI could be helpful in predicting the progression from MCI to AD	Choi et al., 2011
	Human	Depression	ELISA	Elevated plasma LCN2 levels in depressed subjects	LCN2 plasma levels are increased in depressed older persons, resistant to antidepressant medication and age; plasma LCN2 is a possible biomarker for late-life depression	Naudé et al., 2013
	Mouse/human	Multiple sclerosis (MS)	IF, IHC, ELISA, qRT-PCR	LCN2 expression strongly induced after murine MS model and in human blood-cerebrospinal fluid samples of MS patients	LCN2 a valuable molecule for the diagnostics and monitoring of MS	Marques et al., 2012
Pancreas	Human	Pancreatitis	ELISA	Urinary LCN2 levels associated with increased severity and mortality	LCN2 a promising diagnostic and prognostic factor for severe acute pancreatitis in an early stage of the disease	Lipinski et al., 2015
	Human	Chronic pancreatitis, pancreatic cancer	ELISA	LCN2 significantly elevated in the pancreatic juice of patients	LCN2 could help establish etiology for pancreatitis	Kaur et al., 2013
Lung	Mouse	LPS-induced acute lung injury	ELISA, WB, qRT-PCR	LCN2 levels upregulated in diseased mice	LCN2 is a promising in detection of experiment acute lung injury	Zeng et al., 2014
	Human	Sepsis-induced acute respiratory distress syndrome	qRT-PCR	Significantly elevated LCN2 mRNA expression	LCN2 with other neutrophil related genes participates in neutrophil-related mechanisms in progression to acute respiratory distress syndrome	Kangelaris et al., 2015
Musculo-skeletal tissues	Human	Rheumatoid arthritis	ELISA	LCN2 was highly expressed in the synovial fluids of patients compared to healthy controls	LCN2 is a possible diagnostic marker for rheumatoid arthritis	Bläser et al., 1995
Skin	Mouse	Topical psoriasiform skin	NA	LCN2 enhances expression of Th17 cytokines/chemokines and antimicrobial peptides	LCN2 potentiates the development of psoriasis	Hau et al., 2016
Cancer	Human	Brain tumor	Zymography, ELISA, IHC	Great increase of LCN2 in tumor tissue and clearing after tumor resection	Useful predictor of the presence of brain tumors	Smith et al., 2008
	Human	Gastric cancer	MMP-9/LCN2 complex zymography, WB, IHC, IF	Enhance expression of MMP-9/LCN2 in cancer tissue	Enhanced levels of MMP-9/LCN2 complex is highly prognostic for worse survival in gastric cancer patients	Kubben et al., 2007
	Human	Pancreatic adenocarcinoma	IHC, ELISA, qRT-PCR, WB	LCN2 overexpression in pancreatic cancer lesions	LCN2 might participate in pancreatic cell transdifferentiation and progress of cancer	Moniaux et al., 2008
	Human	HCC	IHC	Upregulated LCN2 expression in HCC significantly correlated with unfavorable clinicopathologic features	LCN2 could serve as prognostic factor and potential therapeutic target in HCC	Zhang et al., 2012
	Human	Endometrial cancer	IHC	LCN2 expression was associated with VEGF-A expression and distant tumor recurrences	LCN2 expression is associated with aggressive features and poor prognosis of endometrial cancer	Mannelqvist et al., 2012
	Human	Breast cancer	IHC, ELISA	Elevated LCN2 levels were found at advanced breast cancer stages in breast tissue and urine	LCN2 promotes breast cancer progression by inducing EMT	Yang et al., 2009
	Mouse	Breast cancer model and cell culture models	ELISA	LCN2 contributes to early events in metastasis, induces EMT, enhances migration and invasion	Tumor stroma-derived LCN2 promotes breast cancer metastasis	Ören et al., 2016

AD, Alzheimer's disease; AKI, acute kidney injury; ELISA, Enzyme-linked immunosorbent assay; EMT, epithelial to mesenchymal transition; IF, immunofluoresence; IHC, immuohistochemistry; MCI, mild cognitive impairment; MS, Multiple sclerosis; qRT-PCR, quantitative real time polymerase chain reaction; WB, Western blot.