In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 10 ( 2021-10-21), p. e0258856-
Abstract:
Hypoxia is a common pathway to the progression of end-stage kidney disease. Retinoic acid-inducible gene I (RIG-I) encodes an RNA helicase that recognizes viruses including SARS-CoV2, which is responsible for the production of interferon (IFN)-α/β to prevent the spread of viral infection. Recently, RIG-I activation was found under hypoxic conditions, and klotho deficiency was shown to intensify the activation of RIG-I in mouse brains. However, the roles of these functions in renal inflammation remain elusive. Here, for in vitro study, the expression of RIG-I and IFN-α/β was examined in normal rat kidney (NRK)-52E cells incubated under hypoxic conditions (1% O 2 ). Next, siRNA targeting RIG-I or scramble siRNA was transfected into NRK52E cells to examine the expression of RIG-I and IFN-α/β under hypoxic conditions. We also investigated the expression levels of RIG-I and IFN-α/β in 33 human kidney biopsy samples diagnosed with IgA nephropathy. For in vivo study, we induced renal hypoxia by clamping the renal artery for 10 min in wild-type mice (WT mice) and Klotho-knockout mice (Kl −/− mice). Incubation under hypoxic conditions increased the expression of RIG-I and IFN-α/β in NRK52E cells. Their upregulation was inhibited in NRK52E cells transfected with siRNA targeting RIG-I. In patients with IgA nephropathy, immunohistochemical staining of renal biopsy samples revealed that the expression of RIG-I was correlated with that of IFN-α/β (r = 0.57, P 〈 0.001, and r = 0.81, P 〈 0.001, respectively). The expression levels of RIG-I and IFN-α/β were upregulated in kidneys of hypoxic WT mice and further upregulation was observed in hypoxic Kl −/− mice. These findings suggest that hypoxia induces the expression of IFN-α/β through the upregulation of RIG-I, and that klotho deficiency intensifies this hypoxia-induced expression in kidneys.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0258856
DOI:
10.1371/journal.pone.0258856.g001
DOI:
10.1371/journal.pone.0258856.g002
DOI:
10.1371/journal.pone.0258856.g003
DOI:
10.1371/journal.pone.0258856.g004
DOI:
10.1371/journal.pone.0258856.g005
DOI:
10.1371/journal.pone.0258856.g006
DOI:
10.1371/journal.pone.0258856.g007
DOI:
10.1371/journal.pone.0258856.s001
DOI:
10.1371/journal.pone.0258856.s002
DOI:
10.1371/journal.pone.0258856.s003
DOI:
10.1371/journal.pone.0258856.s004
DOI:
10.1371/journal.pone.0258856.s005
DOI:
10.1371/journal.pone.0258856.s006
DOI:
10.1371/journal.pone.0258856.s007
DOI:
10.1371/journal.pone.0258856.s008
DOI:
10.1371/journal.pone.0258856.s009
DOI:
10.1371/journal.pone.0258856.s010
DOI:
10.1371/journal.pone.0258856.r001
DOI:
10.1371/journal.pone.0258856.r002
DOI:
10.1371/journal.pone.0258856.r003
DOI:
10.1371/journal.pone.0258856.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
Permalink