Growth Differentiation Factor 15 Ameliorates Anti-Glomerular Basement Membrane Glomerulonephritis in Mice

Moschovaki-Filippidou, Foteini; Steiger, Stefanie; Lorenz, Georg; Schmaderer, Christoph; Ribeiro, Andrea; Rauchhaupt, Ekaterina von; Cohen, Clemens D.; Anders, Hans-Joachim; Lindenmeyer, Maja and Lech, Maciej (2020): Growth Differentiation Factor 15 Ameliorates Anti-Glomerular Basement Membrane Glomerulonephritis in Mice. In: International Journal of Molecular Sciences, Vol. 21, No. 19, 6978

Abstract

Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-beta (TGF-beta) cytokine family and an inflammation-associated protein. Here, we investigated the role of GDF15 in murine anti-glomerular basement membrane (GBM) glomerulonephritis. Glomerulonephritis induction in mice induced systemic expression of GDF15. Moreover, we demonstrate the protective effects for GDF15, as GDF15-deficient mice exhibited increased proteinuria with an aggravated crescent formation and mesangial expansion in anti-GBM nephritis. Herein, GDF15 was required for the regulation of T-cell chemotactic chemokines in the kidney. In addition, we found the upregulation of the CXCR3 receptor in activated T-cells in GDF15-deficient mice. These data indicate that CXCL10/CXCR3-dependent-signaling promotes the infiltration of T cells into the organ during acute inflammation controlled by GDF15. Together, these results reveal a novel mechanism limiting the migration of lymphocytes to the site of inflammation during glomerulonephritis.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• Language: English