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

Abstract

Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) 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.

Macrophage-Specific MCPIP1/Regnase-1 Attenuates Kidney Ischemia-Reperfusion Injury by Shaping the Local Inflammatory Response and Tissue Regeneration

“…This is in line with previous studies showing that Mcpip1 knockdown aggravates liver IRI in mice [35]. Thus, MCPIP1 acts as a negative regulator of immune responses in the kidney [41,42,[51][52][53]]. Yet, various negative regulators display unique signaling abilities and may function in different cells, processes, and phases of inflammatory response.…”

Urinary proteomics investigations into contrast-induced acute kidney injury

“…Moreover, GDF15-deficient mice showed increased levels of the CXCR3 receptor in activated T cells and increased levels of proteinuria with aggravated crescent formation and mesangial expansion in anti-GBM nephritis. This study suggested that CXCL10/CXCR3-dependent signalling promotes T cell infiltration into the organ during GDF15-regulated acute inflammatory processes [ 34 ]. Thus, GDF15 has important value for further investigation.…”

Kidney Inflammation, Injury and Regeneration 2020

“…In this current Special Edition, thirteen original research articles are presented: twelve in vivo studies in a murine or rat model and one in vitro study [ 3 ]. Seven studies show results from AKI models [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ], five from fibrosis models (or CKD models) [ 9 , 11 , 12 , 13 , 14 ] and two from a transplant rejection model [ 4 , 15 ] (two studies used two different in vivo models).…”

“…Others used an IR model to show that the NOX1-selective inhibition attenuates kidney IR injuries via the downregulation of oxidative stress-mediated kinase signaling [ 8 ] or to investigate the autophagy dynamics during an IR injury, a potential treatment strategy due to removing damaged cells, macromolecules and organelles [ 6 ]. The effect of growth differentiation factor 15 (GDF15) was investigated in a murine model of anti-glomerular basement membrane glomerulonephritis [ 7 ]. The study showed that GDF15 is required for the regulation of T-cell chemotactic chemokines in the kidneys and demonstrated the protective effects of GDF15.…”

“…The study showed that GDF15 is required for the regulation of T-cell chemotactic chemokines in the kidneys and demonstrated the protective effects of GDF15. The study revealed a novel mechanism limiting the migration of lymphocytes to the site of inflammation during glomerulonephritis [ 7 ]. The findings of Nežić and coworkers investigated the molecular mechanism involved in the reno-protective effects of simvastatin in an endotoxin-induced AKI model [ 5 ].…”