Macrophage-secreted lipocalin-2 promotes regeneration of injured primary murine renal tubular epithelial cells

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DOI

  • Anja Urbschat
  • Anne Kathrin Thiemens, Goethe University Frankfurt
  • ,
  • Christina Mertens, Goethe University Frankfurt
  • ,
  • Claudia Rehwald, Goethe University Frankfurt
  • ,
  • Julia K. Meier, Goethe University Frankfurt
  • ,
  • Patrick C. Baer, Goethe University Frankfurt
  • ,
  • Michaela Jung, Goethe University Frankfurt

Lipocalin-2 (Lcn-2) is rapidly upregulated in macrophages after renal tubular injury and acts as renoprotective and pro-regenerative agent. Lcn-2 possesses the ability to bind and transport iron with high affinity. Therefore, the present study focuses on the decisive role of the Lcn-2 iron-load for its pro-regenerative function. Primary mouse tubular epithelial cells were isolated from kidney tissue of wildtype mice and incubated with 5μM Cisplatin for 24h to induce injury. Bone marrow-derived macrophages of wildtype and Lcn-2-/- mice were isolated and polarized with IL-10 towards an anti-inflammatory, iron-release phenotype. Their supernatants as well as recombinant iron-loaded holo-Lcn-2 was used for stimulation of Cisplatin-injured tubular epithelial cells. Incubation of tubular epithelial cells with wildtype supernatants resulted in less damage and induced cellular proliferation, whereas in absence of Lcn-2 no protective effect was observed. Epithelial integrity as well as cellular proliferation showed a clear protection upon rescue experiments applying holo-Lcn-2. Notably, we detected a positive correlation between total iron amounts in tubular epithelial cells and cellular proliferation, which, in turn, reinforced the assumed link between availability of Lcn-2-bound iron and recovery. We hypothesize that macrophage-released Lcn-2-bound iron is provided to tubular epithelial cells during toxic cell damage, whereby injury is limited and recovery is favored.

Original languageEnglish
Article number2038
JournalInternational Journal of Molecular Sciences
Volume21
Issue6
Number of pages17
ISSN1661-6596
DOIs
Publication statusPublished - 2 Mar 2020

    Research areas

  • Iron, Lipocalin-2, Macrophages, Renal tubular epithelial cells

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