Possible role of complement factor H in podocytes in clearing glomerular subendothelial immune complex deposits.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 05 2019
27 05 2019
Historique:
received:
16
08
2018
accepted:
15
05
2019
entrez:
29
5
2019
pubmed:
28
5
2019
medline:
21
10
2020
Statut:
epublish
Résumé
Podocytes are known to express various complement factors including complement factor H (CFH) and to promote the removal of both subendothelial and subepithelial immune complex (IC) deposits. Using podocyte-selective injury model NEP25 mice and an IgG3-producing hybridoma clone 2B11.3 established by MRL/lpr mice, the present study investigated the role of podocyte complement regulation in only subendothelial IC deposition. In immunotoxin (LMB2) induced fatal podocyte injury (NEP25/LMB2) at day 12, glomerular CFH and C3a receptor (C3aR) expression was decreased as compared with NEP25/vehicle mice. In contrast, in sublytic podocyte injury 5 days after LMB2, glomerular CFH and C3aR expression was increased as compared with NEP25/vehicle mice. Intra-abdominal injection of 2B11.3 hybridoma to NEP25 mice (NEP25/hybridoma) caused IC deposition limited to the subendothelial area associated with unaltered CFH expression. NEP25/hybridoma mice with sublytic podocyte injury (NEP25/hybridoma/LMB2) resulted in increased glomerular CFH expression (1.7-fold) accompanied by decreased subendothelial IC deposition, as compared with NEP25/hybridoma. Immunostaining revealed that CFH was dominantly expressed in podocytes of NEP25/hybridoma/LMB2. In addition, puromycin-induced sublytic podocyte injury promoted CFH expression in immortalized mouse podocytes in vitro. These results suggest that in response to sublytic levels of injury, podocyte induced CFH expression locally and clearance of subendothelial IC deposits.
Identifiants
pubmed: 31133737
doi: 10.1038/s41598-019-44380-3
pii: 10.1038/s41598-019-44380-3
pmc: PMC6536504
doi:
Substances chimiques
Antigen-Antibody Complex
0
Complement Factor H
80295-65-4
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7857Références
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