Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease

Guillaume Courbon, Connor Francis, Claire Gerber, Samantha Neuburg, Xueyan Wang, Emily Lynch, Tamara Isakova, Jodie L. Babitt, Myles S Wolf, Aline Martin, Valentin David*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Bone-produced fibroblast growth factor 23 (FGF23) increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2; LCN2 the murine homolog) is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD progression. We investigated bone FGF23 regulation by circulating LCN2. At 23 weeks, Col4a3KO mice showed impaired kidney function, increased levels of kidney and serum LCN2, increased bone and serum FGF23, anemia, and left ventricular hypertrophy (LVH). Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum FGF23. Lcn2 deletion specifically prevented FGF23 elevations in response to inflammation, but not iron deficiency or phosphate, and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone cells. These results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in CKD. LCN2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.

Original languageEnglish (US)
Article number35
JournalBone Research
Volume9
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

Fingerprint

Dive into the research topics of 'Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease'. Together they form a unique fingerprint.

Cite this