Klotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys.

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,...

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Autores principales:	Asako Urabe, Shigehiro Doi, Ayumu Nakashima, Takeshi Ike, Kenichi Morii, Kensuke Sasaki, Toshiki Doi, Koji Arihiro, Takao Masaki
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0fbdc8bf39ef4ebf97e54d1a9a7eb769
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spelling	oai:doaj.org-article:0fbdc8bf39ef4ebf97e54d1a9a7eb7692021-12-02T20:16:40ZKlotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys.1932-620310.1371/journal.pone.0258856https://doaj.org/article/0fbdc8bf39ef4ebf97e54d1a9a7eb7692021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258856https://doaj.org/toc/1932-6203Hypoxia 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% O2). 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.Asako UrabeShigehiro DoiAyumu NakashimaTakeshi IkeKenichi MoriiKensuke SasakiToshiki DoiKoji ArihiroTakao MasakiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258856 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Asako Urabe Shigehiro Doi Ayumu Nakashima Takeshi Ike Kenichi Morii Kensuke Sasaki Toshiki Doi Koji Arihiro Takao Masaki Klotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys.
description	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% O2). 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.
format	article
author	Asako Urabe Shigehiro Doi Ayumu Nakashima Takeshi Ike Kenichi Morii Kensuke Sasaki Toshiki Doi Koji Arihiro Takao Masaki
author_facet	Asako Urabe Shigehiro Doi Ayumu Nakashima Takeshi Ike Kenichi Morii Kensuke Sasaki Toshiki Doi Koji Arihiro Takao Masaki
author_sort	Asako Urabe
title	Klotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys.
title_short	Klotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys.
title_full	Klotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys.
title_fullStr	Klotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys.
title_full_unstemmed	Klotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys.
title_sort	klotho deficiency intensifies hypoxia-induced expression of ifn-α/β through upregulation of rig-i in kidneys.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/0fbdc8bf39ef4ebf97e54d1a9a7eb769
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Klotho deficiency intensifies hypoxia-induced expression of IFN-α/β through upregulation of RIG-I in kidneys.

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