Lipocalin-2 abrogates epithelial cell cycle arrest by PPARγ inhibition.
Lab Invest
; 98(11): 1408-1422, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-30087458
ABSTRACT
Macrophage-epithelial cross-talk regulates cell cycle progression and represents an important factor in rescuing epithelial cells from cell cycle arrest in order to maintain a healthy epithelial phenotype. However, the underlying mechanisms are still not well defined. We provide evidence that macrophage-secreted lipocalin-2 (Lcn-2) plays a key role during this process. In a co-culture setup using cell cycle arrested NRK52e renal epithelial cells and primary bone marrow-derived macrophages, Lcn-2 restores proliferation through inhibition of peroxisome proliferator-activated receptor (PPAR)-γ. Lcn-2 overexpression in macrophages overcomes epithelial cell cycle arrest and enhances epithelial markers via megalin and the downstream activation of PI3K/Akt signalling pathway, whereas a knockdown of Lcn-2 in macrophages prevented this effect. Our results show that macrophage-secreting Lcn-2 is crucial in rescuing epithelial cells from cell cycle arrest and in promoting epithelial proliferation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
PPAR gama
/
Proliferação de Células
/
Células Epiteliais
/
Lipocalina-2
Limite:
Animals
Idioma:
En
Revista:
Lab Invest
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha