RGD Reference Report - Induction of neutrophil gelatinase-associated lipocalin in vascular injury via activation of nuclear factor-kappaB. - Rat Genome Database

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Induction of neutrophil gelatinase-associated lipocalin in vascular injury via activation of nuclear factor-kappaB.

Authors: Bu, DX  Hemdahl, AL  Gabrielsen, A  Fuxe, J  Zhu, C  Eriksson, P  Yan, ZQ 
Citation: Bu DX, etal., Am J Pathol. 2006 Dec;169(6):2245-53.
RGD ID: 2316510
Pubmed: PMID:17148685   (View Abstract at PubMed)
PMCID: PMC1762469   (View Article at PubMed Central)

Neutrophil gelatinase-associated lipocalin (NGAL) has recently emerged as an important modulator of cell homeostasis. Elevated plasma NGAL levels, possibly because of activation of blood leukocytes, are associated with atherosclerosis. However, little is known about induction of NGAL expression in blood vessels. Using a rat carotid artery injury model, we found that NGAL was highly induced in the intima after angioplasty but was attenuated by adenovirus-mediated expression of a dominant-negative mutant of inhibitor of nuclear factor (NF)-kappaB kinase beta (dnIKKbeta). Expression of NGAL mRNA and protein was also up-regulated in an NF-kappaB-dependent manner in rat and human vascular smooth muscle cells (SMCs) in response to interleukin-1beta stimulation. Rat SMC-produced NGAL was present as mono- and homomeric forms in the cytosol and in a complex containing matrix metalloproteinase-9 (MMP-9) after secretion. In agreement with levels of NGAL, proteolytic activity of MMP-9 was markedly high in the intima of injured vessels and in the culture supernatant of activated intimal SMCs but was reduced in the vessels transduced with dnIKKbeta. The present study reveals a previously unrecognized vascular response to an-gioplastic injury, characterized by NF-kappaB-dependent expression of NGAL in vascular SMCs. Further-more, SMC-produced NGAL interacts with MMP-9, a mechanism by which NGAL may modulate MMP-9 proteolytic activity in the vascular repair process.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
identical protein binding  IPILcn2 (Rattus norvegicus)2316510homodimerization and homotrimerizationRGD 
protease binding  IPIMmp9 (Rattus norvegicus)2316510 RGD 
protein binding  IPILcn2 (Rattus norvegicus)2316510 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lcn2  (lipocalin 2)
Mmp9  (matrix metallopeptidase 9)


Additional Information