Your browser doesn't support javascript.
Klotho deficiency intensifies hypoxia-induced expression of IFN-α/ß through upregulation of RIG-I in kidneys.
Urabe, Asako; Doi, Shigehiro; Nakashima, Ayumu; Ike, Takeshi; Morii, Kenichi; Sasaki, Kensuke; Doi, Toshiki; Arihiro, Koji; Masaki, Takao.
  • Urabe A; Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
  • Doi S; Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
  • Nakashima A; Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
  • Ike T; Department of Stem Cell Biology and Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Morii K; Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
  • Sasaki K; Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
  • Doi T; Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
  • Arihiro K; Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.
  • Masaki T; Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan.
PLoS One ; 16(10): e0258856, 2021.
Article in English | MEDLINE | ID: covidwho-1542176
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/ß 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/ß was examined in normal rat kidney (NRK)-52E cells incubated under hypoxic conditions (1% O2). Next, siRNA targeting RIG-I or scramble siRNA was transfected into NRK52E cells to examine the expression of RIG-I and IFN-α/ß under hypoxic conditions. We also investigated the expression levels of RIG-I and IFN-α/ß 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/ß 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/ß (r = 0.57, P<0.001, and r = 0.81, P<0.001, respectively). The expression levels of RIG-I and IFN-α/ß 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/ß through the upregulation of RIG-I, and that klotho deficiency intensifies this hypoxia-induced expression in kidneys.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Up-Regulation / Interferon-alpha / RNA Helicases / Glucuronidase / Kidney / Hypoxia Limits: Animals Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Journal.pone.0258856

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Up-Regulation / Interferon-alpha / RNA Helicases / Glucuronidase / Kidney / Hypoxia Limits: Animals Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Journal.pone.0258856