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Lab Invest. 2018 Nov;98(11):1408-1422. doi: 10.1038/s41374-018-0098-4. Epub 2018 Aug 7.

Lipocalin-2 abrogates epithelial cell cycle arrest by PPARγ inhibition.

Author information

1
Institute of Biochemistry I, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
2
Department of Experimental Nephrology, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
3
Department of Ischemia and Inflammation, IIBB-CSIC-IDIBAPS, Rosselló, 161, 7th floor, 08036, Barcelona, Spain.
4
CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.
5
Department of Experimental Nephrology, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain. asola@idibell.cat.
6
CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. asola@idibell.cat.

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.

PMID:
30087458
DOI:
10.1038/s41374-018-0098-4

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