RT info:eu-repo/semantics/article
T1 Biglycan Is a Novel Mineralocorticoid Receptor Target Involved in Aldosterone/Salt-Induced Glomerular Injury
A1 Nakamura, Toshifumi
A1 Bonnard, Benjamin
A1 Palacios-Ramirez, Roberto
A1 Fernández-Celis, Amaya
A1 Jaisser, Frédéric
A1 López-Andrés, Natalia
K1 C-C motif chemokine ligand 3 (CCL3)
K1 biglycan
K1 glomerular injury
K1 mineralocorticoid receptor
K1 proteoglycan
K1 toll-like receptor 4 (TLR4)
AB The beneficial effects of mineralocorticoid receptor (MR) antagonists (MRAs) for various kidney diseases are established. However, the underlying mechanisms of kidney injury induced by MR activation remain to be elucidated. We recently reported aldosterone-induced enhancement of proteoglycan expression in mitral valve interstitial cells and its association with fibromyxomatous valvular disorder. As the expression of certain proteoglycans is elevated in several kidney diseases, we hypothesized that proteoglycans mediate kidney injury in the context of aldosterone/MR pathway activation. We evaluated the proteoglycan expression and tissue injury in the kidney and isolated glomeruli of uninephrectomy/aldosterone/salt (NAS) mice. The MRA eplerenone was administered to assess the role of the MR pathway. We investigated the direct effects of biglycan, one of the proteoglycans, on macrophages using isolated macrophages. The kidney samples from NAS-treated mice showed enhanced fibrosis and increased expression of biglycan accompanying glomerular macrophage infiltration and enhanced expression of TNF-α, iNOS, Nox2, CCL3 (C-C motif chemokine ligand 3), and phosphorylated NF-κB. Eplerenone blunted these changes. Purified biglycan stimulated macrophages to express TNF-α, iNOS, Nox2, and CCL3. This was prevented by a toll-like receptor 4 (TLR4) or NF-κB inhibitor, indicating that biglycan stimulation is dependent on the TLR4/NF-κB pathway. We identified the proteoglycan biglycan as a novel target of MR involved in MR-induced glomerular injury and macrophage infiltration via a biglycan/TLR4/NF-κB/CCL3 cascade
PB MDPI
SN 1422-0067
YR 2022
FD 2022-06-15
LK https://uvadoc.uva.es/handle/10324/66274
UL https://uvadoc.uva.es/handle/10324/66274
LA eng
NO Int J Mol Sci. 2022 Jun 15
NO Producción Científica
DS UVaDOC
RD 28-nov-2024