In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 11 ( 2021-11-29), p. e0260449-
Abstract:
The influence of excess salt intake on acute kidney injury (AKI) has not been examined precisely except for some clinical data, unlike in chronic kidney disease. Here, we addressed the influence of high salt (HS) on AKI and its underlying mechanisms in terms of the activity of circulating apoptosis inhibitor of macrophage (AIM, also called CD5L) protein, a facilitator of AKI repair. HS loading in mice subjected to ischemia/reperfusion (IR) resulted in high mortality with advanced renal tubular obstruction and marked exacerbation in biomarkers of proximal renal tubular damage. This AKI exacerbation appeared to be caused mainly by the reduced AIM dissociation from IgM pentamer in serum, as IgM-free AIM is indispensable for the removal of intratubular debris to facilitate AKI repair. Injection of recombinant AIM (rAIM) ameliorated the AKI induced by IR/HS, dramatically improving the tubular damage and mouse survival. The repair of lethal AKI by AIM was dependent on AIM/ kidney injury molecule-1 (KIM-1) axis, as rAIM injection was not effective in KIM-1 deficient mice. Our results demonstrate that the inhibition of AIM dissociation from IgM is an important reason for the exacerbation of AKI by HS, that AIM is a strong therapeutic tool for severe AKI.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0260449
DOI:
10.1371/journal.pone.0260449.g001
DOI:
10.1371/journal.pone.0260449.g002
DOI:
10.1371/journal.pone.0260449.g003
DOI:
10.1371/journal.pone.0260449.g004
DOI:
10.1371/journal.pone.0260449.s001
DOI:
10.1371/journal.pone.0260449.s002
DOI:
10.1371/journal.pone.0260449.s003
DOI:
10.1371/journal.pone.0260449.s004
DOI:
10.1371/journal.pone.0260449.s005
DOI:
10.1371/journal.pone.0260449.s006
DOI:
10.1371/journal.pone.0260449.r001
DOI:
10.1371/journal.pone.0260449.r002
DOI:
10.1371/journal.pone.0260449.r003
DOI:
10.1371/journal.pone.0260449.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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