Sphingosine-1-phosphate signalling induces the production of Lcn-2 by macrophages to promote kidney regeneration.
Inflammatory reactions are initiated to eliminate pathogens, but also to promote repair of damaged tissue after acute inflammation is terminated. In this regard, macrophages play a prominent role during induction as well as resolution of inflammation and injury in various organs including the kidney. The present study describes a mechanism for renal tissue regeneration after ischaemia/reperfusion injury. Following injury, apoptotic cell-derived sphingosine-1-phosphate (S1P) or exogenously administered sphingosine analogue FTY720 activates macrophages to support the proliferation and healing of renal epithelium, once inflammatory conditions are terminated. Both suppression of inflammation and renal regeneration might require S1P receptor 3 (S1P3) signalling and downstream release of neutrophil gelatinase-associated lipocalin (NGAL/Lcn-2) from macrophages. Overall, our data point to a macrophage-dependent S1P-S1P3-Lcn-2 axis that might be beneficial for restoration of kidney function after an ischaemic insult.
CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. asmbam@iibb.csic.es
Anna
A
Sola
Andreas
A
Weigert
Michaela
M
Jung
Eugenia
E
Vinuesa
Kerstin
K
Brecht
Nicole
N
Weis
Bernhard
B
Brüne
Niels
N
Borregaard
Georgina
G
Hotter
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D015513:Oncogene Proteins / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors
D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D008246:Lysophospholipids; D015513:Oncogene Proteins; D049349:Receptors, Lysosphingolipid; C501285:S1pr3 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; C071332:Lcn2 protein, mouse; C060506:sphingosine 1-phosphate; D013110:Sphingosine