Table 1.

Murine studies on netrin-1 and its receptors in acute inflammation.

Acute Inflammation
Model	Receptor	Netrin-1 Expression	Outcome	Ref.
Lung Inflammation
S. aureus pneumonia in mice	Unc5b	⇓	Netrin-1 expression is attenuated in S. aureus septicemia.	[20]
LPS and ventilator induced lung injury in mice	Adora2b	⇓	Netrin-1 expression is attenuated by inflammation, and netrin-1 limits neutrophil influx into the lung.	[29]
LPS induced lung injury in pigs		not defined	Intravenous and inhalative netrin-1 mitigated pulmonary inflammation and lung damage.	[30]
Mouse model with LIRI	Adora2b	⇓	Positive correlation between netrin-1 expression and Treg cell population.	[31]
An ALI model was established by intratracheal instillation of LPS in C57BL/J mice	Adora2b	⇓	Receptor binding has the potential to enhance ENaC-dependent alveolar fluid clearance by supplementation of netrin-1.	[32]
Hypobaric hypoxia-induced lung injury in mice	UNC5HB	⇓	Pretreatment of netrin-1 dampen ALI and inhibits neutrophil migration.	[33]
Abdominal Inflammation
Colitis
DSS-induced colitis	Adora2b	⇑ in colon	Netrin-1 is induced during acute colitis limits neutrophil influx into the colonic epithelium.	[34]
Peritonitis
ZyA-induced peritonitis	Adora2b	⇓	Netrin-1 expression is reduced during peritonitis. Exogenous netrin-1 application attenuates inflammation.	[35]
ZyA-induced peritonitis	Adora2b		Netrin-1 synergistically interacts with RvD2 in an anti-inflammatory and pro-resolving fashion.	[27]
Pancreatitis
L-arginine-induced acute pancreatitis	not defined	⇓	Netrin-1 administration reduced pancreas and lung injury.	[36]
Acute Kidney Injury
Ischemia–reperfusion-induced AKI	not defined	⇑ protein levels in renal tissue mRNA in renal tissue protein and mRNA levels in intestine	Netrin-1 is induced in renal tissue following IR. Ntn1 administration attenuates renal failure and kidney inflammation.	[37]
Ischemia–reperfusion-induced AKI	not defined	not defined	Netrin-1 overexpression attenuates renal failure by decreased apoptosis and increased tubular epithelium proliferation.	[38]
Ischemia–reperfusion-induced AKI	Unc5b	⇓ mRNA in renal tissue	Netrin-1 overexpression attenuates renal failure and systemic inflammation.	[39]
Ischemia–reperfusion-induced AKI	not defined	⇑ renal tissue	Netrin-1 attenuates renal failure and systemic inflammation.	[40]
Ischemia–reperfusion-induced AKI	not defined	not defined	Netrin-1 attenuates renal failure and promotes M2 polarization through PPARγ.	[16]
Hypoxia
In vivo hypoxia	Adora2b	⇑ in lung and colon via HIF-1α	Netrin-1 attenuates systemic inflammation and neutrophil recruitment.	[13]
Liver-Ischemia Reperfusion
	Adora2b	⇓ in liver	Netrin-1 attenuates neutrophil recruitment, local and systemic inflammation and promotes resolution and tissue regeneration.	[28]
Myocardial Infarct
Normothermic ischemia reperfusion Langendorff perfusion	DCC	not defined	Netrin-1 pre- and postconditioning decrease infarct size and attenuate myocardiocyte apoptosis through ERK1/2 and NO induction.	[41,42,43]
Heterotopic cardiac transplant with 8 h of cold ischemia		⇓	Netrin-1 protects from reperfusion injury by limiting leukocyte influx, cardiomyocyte apoptosis, and M2 macrophage polarization through PPARg.	[44]
Chronic LAD coronary ligation	not defined	not defined	Intracardial application of netrin-1-transduced mesenchymal stem cells attenuated infarction size and prevented cardiac hypertrophic remodeling.	[45]
Normothermic ischemia reperfusion Langendorff perfusion	not defined	not defined	Netrin-1 preconditioning attenuates infarcts size by preventing superoxide and NADPH oxidase production, preventing mitochondrial dysfunction.	[46]