Macrophage-Secreted Lipocalin-2 Promotes Regeneration of Injured Primary Murine Renal Tubular Epithelial Cells

Urbschat, Anja; Thiemens, Anne-Kathrin; Mertens, Christina; Rehwald, Claudia; Meier, Julia K.; Baer, Patrick C.; Jung, Michaela

doi:10.3390/ijms21062038

Open AccessArticle

Macrophage-Secreted Lipocalin-2 Promotes Regeneration of Injured Primary Murine Renal Tubular Epithelial Cells

by

Anja Urbschat

¹,

Anne-Kathrin Thiemens

²,

Christina Mertens

³,

Claudia Rehwald

³,

Julia K. Meier

³,

Patrick C. Baer

^2,†

and

Michaela Jung

^3,*,†

¹

Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark

²

Division of Nephrology, Department of Internal Medicine III, Goethe-University Frankfurt, 60323 Frankfurt am Main, Germany

³

Institute of Biochemistry I, Goethe-University Frankfurt, Faculty of Medicine, 60323 Frankfurt am Main, Germany

^*

Author to whom correspondence should be addressed.

^†

Theses authors contributed equally to this work.

Int. J. Mol. Sci. 2020, 21(6), 2038; https://doi.org/10.3390/ijms21062038

Submission received: 11 February 2020 / Revised: 12 March 2020 / Accepted: 13 March 2020 / Published: 16 March 2020

(This article belongs to the Special Issue Kidney Inflammation, Injury and Regeneration 2020)

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Abstract

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 5 µM Cisplatin for 24 h 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.

Keywords: renal tubular epithelial cells; macrophages; lipocalin-2; iron

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MDPI and ACS Style

Urbschat, A.; Thiemens, A.-K.; Mertens, C.; Rehwald, C.; Meier, J.K.; Baer, P.C.; Jung, M. Macrophage-Secreted Lipocalin-2 Promotes Regeneration of Injured Primary Murine Renal Tubular Epithelial Cells. Int. J. Mol. Sci. 2020, 21, 2038. https://doi.org/10.3390/ijms21062038

AMA Style

Urbschat A, Thiemens A-K, Mertens C, Rehwald C, Meier JK, Baer PC, Jung M. Macrophage-Secreted Lipocalin-2 Promotes Regeneration of Injured Primary Murine Renal Tubular Epithelial Cells. International Journal of Molecular Sciences. 2020; 21(6):2038. https://doi.org/10.3390/ijms21062038

Chicago/Turabian Style

Urbschat, Anja, Anne-Kathrin Thiemens, Christina Mertens, Claudia Rehwald, Julia K. Meier, Patrick C. Baer, and Michaela Jung. 2020. "Macrophage-Secreted Lipocalin-2 Promotes Regeneration of Injured Primary Murine Renal Tubular Epithelial Cells" International Journal of Molecular Sciences 21, no. 6: 2038. https://doi.org/10.3390/ijms21062038

APA Style

Urbschat, A., Thiemens, A.-K., Mertens, C., Rehwald, C., Meier, J. K., Baer, P. C., & Jung, M. (2020). Macrophage-Secreted Lipocalin-2 Promotes Regeneration of Injured Primary Murine Renal Tubular Epithelial Cells. International Journal of Molecular Sciences, 21(6), 2038. https://doi.org/10.3390/ijms21062038

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Macrophage-Secreted Lipocalin-2 Promotes Regeneration of Injured Primary Murine Renal Tubular Epithelial Cells

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