Ablation of Myeloid Cell MRP8 Ameliorates Nephrotoxic Serum-induced Glomerulonephritis by Affecting Macrophage Characterization through Intraglomerular Crosstalk.
Animals
Calgranulin A
/ deficiency
Cell Lineage
Disease Models, Animal
Gene Deletion
Glomerulonephritis
/ metabolism
Integrases
/ metabolism
Kidney Glomerulus
/ pathology
Lectins, C-Type
/ metabolism
Macrophages
/ metabolism
Membrane Proteins
/ metabolism
Mesangial Cells
/ metabolism
Mice
Mice, Knockout
Myeloid Progenitor Cells
/ metabolism
RAW 264.7 Cells
Recombination, Genetic
/ genetics
Serum
/ metabolism
Stress Fibers
/ metabolism
Toll-Like Receptor 4
/ metabolism
Up-Regulation
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 02 2020
20 02 2020
Historique:
received:
27
11
2019
accepted:
03
02
2020
entrez:
22
2
2020
pubmed:
23
2
2020
medline:
13
11
2020
Statut:
epublish
Résumé
Toll-like receptor 4 (TLR4) and one of its endogenous ligands myeloid-related protein 8 (MRP8 or S100A8), especially expressed in macrophages, play an important role in diabetic nephropathy and autoimmune disorders. However, detailed mechanisms and consequence of MRP8 expression remain unknown, partly due to embryonic lethality of MRP8 knockout mice. In this study, Myeloid lineage cell-specific MRP8 knockout mice were generated, and nephrotoxic serum-induced glomerulonephritis was developed. Mice with conditional ablation of MRP8 gene in myeloid cells exhibited less severe histological damage, proteinuria and inflammatory changes compared to control mice. Mechanism of MRP8 upregulation was investigated using cultured cells. Co-culture of macrophages with mesangial cells or mesangial cell-conditioned media, but not with proximal tubules, markedly upregulated MRP8 gene expression and inflammatory M1 phenotype in macrophages, which was attenuated in MRP8-deleted bone marrow-derived macrophages. Effects of MRP8 deletion was further studied in the context of macrophage-inducible C-type lectin (Mincle), which is critically involved in maintenance of M1 phenotype of macrophages. MRP8 ablation in myeloid cells suppressed the induction of Mincle expression on macrophages in glomerulonephritis. Thus, we propose that intraglomerular crosstalk between mesangial cells and macrophages plays a role in inflammatory changes in glomerulonephritis, and MRP8-dependent Mincle expression in macrophage may be involved in the process.
Identifiants
pubmed: 32080297
doi: 10.1038/s41598-020-59970-9
pii: 10.1038/s41598-020-59970-9
pmc: PMC7033179
doi:
Substances chimiques
Calgranulin A
0
Clecsf8 protein, mouse
0
Lectins, C-Type
0
Membrane Proteins
0
S100a8 protein, mouse
0
Toll-Like Receptor 4
0
Cre recombinase
EC 2.7.7.-
Integrases
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3056Références
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