Fibrocytes develop outside the kidney but contribute to renal fibrosis in a mouse model

Reich, Barbara and Schmidbauer, Kathrin and Gomez, Manuel Rodriguez and Hermann, Fabian Johannes and Goebel, Nicole and Bruehl, Hilke and Ketelsen, Isabel and Talke, Yvonne and Mack, Matthias (2013) Fibrocytes develop outside the kidney but contribute to renal fibrosis in a mouse model. KIDNEY INTERNATIONAL, 84 (1). pp. 78-89. ISSN 0085-2538,

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Abstract

Collagen-producing bone marrow-derived cells (fibrocytes) have been detected in animal models and patients with fibrotic diseases. In vitro data suggest that they develop from monocytes with the help of accessory cells and profibrotic soluble factors. Using a mouse model of renal fibrosis, unilateral ureteral obstruction, we found the number of circulating fibrocytes was not reduced when monocytes were depleted with a monoclonal antibody against CCR2 or when CCR2 -/- mice with very low numbers of circulating or splenic monocytes were analyzed. The absence of CCR2, however, interfered with migration of fibrocytes into the kidney. The phenotype of splenic and renal fibrocytes was very similar and distinct from classical monocytes as fibrocytes expressed no CD115, medium levels of CCR2, and high levels of CD11b and Ly-6G. Using a depleting monoclonal antibody against Ly-6G or bone marrow chimeric mice expressing the diphtheria toxin receptor under the control of CD11b, we could efficiently deplete fibrocytes from the kidney. Depletion of fibrocytes or reduced migration of fibrocytes into the kidney resulted in lower renal expression of collagen-I. Thus, fibrocytes develop outside the kidney independent of infiltrating monocytes and rely on CCR2 for migration into target organs.

Item Type: Article
Uncontrolled Keywords: SERUM AMYLOID-P; INDUCED PULMONARY-FIBROSIS; BONE-MARROW; CIRCULATING FIBROCYTES; LUNG FIBROSIS; CHEMOKINE RECEPTOR-5; INFLAMMATORY SITES; INDUCED ARTHRITIS; DENDRITIC CELLS; LIVER-INJURY; cell ablation; chemokine receptor; fibrosis; immunology
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Innere Medizin II
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Apr 2020 09:04
Last Modified: 07 Apr 2020 09:04
URI: https://pred.uni-regensburg.de/id/eprint/16456

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