Targeting interferon-stimulated gene of 20 kDa protein (Isg20) inhibits ribosome biogenesis to ameliorate the progression of renal fibrosis.

Chronic kidney disease (CKD) is a global health issue that significantly threatens human health, with its incidence increasing annually. Renal fibrosis is characterized by the progressive loss of kidney function, leading to significant morbidity and mortality. Although ribosome biogenesis has been r...

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Main Authors: Xiaoming Liu, Huijuan Wang, Kai Wang, Ying Liu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0322639
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author Xiaoming Liu
Huijuan Wang
Kai Wang
Ying Liu
author_facet Xiaoming Liu
Huijuan Wang
Kai Wang
Ying Liu
author_sort Xiaoming Liu
collection DOAJ
description Chronic kidney disease (CKD) is a global health issue that significantly threatens human health, with its incidence increasing annually. Renal fibrosis is characterized by the progressive loss of kidney function, leading to significant morbidity and mortality. Although ribosome biogenesis has been reported to be increased in several kidney diseases, its role in renal fibrosis remains unclear. This study investigates the role of the interferon-stimulated gene of 20 kDa protein (Isg20), an RNA exonuclease involved in several stages of ribosome biogenesis, in the progression of renal fibrosis. Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets identified upregulation of ribosome biogenesis-related genes and Isg20 expression in renal fibrosis samples. Using the unilateral ureteral obstruction (UUO)-induced renal fibrosis mouse model, we confirmed elevated Isg20 expression, promoted renal fibrosis, and increased ribosome biogenesis. Knockdown of Isg20 significantly reduced ribosome biogenesis, ameliorated kidney damage, inhibited pro-inflammatory cytokines levels and renal fibrotic changes, and decreased endoplasmic reticulum stress and cell apoptosis. Our findings suggest that Isg20 exacerbates renal fibrosis by promoting ribosome biogenesis, ER stress and cell apoptosis highlighting a potential therapeutic target for renal fibrosis treatment.
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spelling doaj-art-6b4698ba98ed4051a3cd38fdba60501a2025-08-20T03:29:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01207e032263910.1371/journal.pone.0322639Targeting interferon-stimulated gene of 20 kDa protein (Isg20) inhibits ribosome biogenesis to ameliorate the progression of renal fibrosis.Xiaoming LiuHuijuan WangKai WangYing LiuChronic kidney disease (CKD) is a global health issue that significantly threatens human health, with its incidence increasing annually. Renal fibrosis is characterized by the progressive loss of kidney function, leading to significant morbidity and mortality. Although ribosome biogenesis has been reported to be increased in several kidney diseases, its role in renal fibrosis remains unclear. This study investigates the role of the interferon-stimulated gene of 20 kDa protein (Isg20), an RNA exonuclease involved in several stages of ribosome biogenesis, in the progression of renal fibrosis. Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets identified upregulation of ribosome biogenesis-related genes and Isg20 expression in renal fibrosis samples. Using the unilateral ureteral obstruction (UUO)-induced renal fibrosis mouse model, we confirmed elevated Isg20 expression, promoted renal fibrosis, and increased ribosome biogenesis. Knockdown of Isg20 significantly reduced ribosome biogenesis, ameliorated kidney damage, inhibited pro-inflammatory cytokines levels and renal fibrotic changes, and decreased endoplasmic reticulum stress and cell apoptosis. Our findings suggest that Isg20 exacerbates renal fibrosis by promoting ribosome biogenesis, ER stress and cell apoptosis highlighting a potential therapeutic target for renal fibrosis treatment.https://doi.org/10.1371/journal.pone.0322639
spellingShingle Xiaoming Liu
Huijuan Wang
Kai Wang
Ying Liu
Targeting interferon-stimulated gene of 20 kDa protein (Isg20) inhibits ribosome biogenesis to ameliorate the progression of renal fibrosis.
PLoS ONE
title Targeting interferon-stimulated gene of 20 kDa protein (Isg20) inhibits ribosome biogenesis to ameliorate the progression of renal fibrosis.
title_full Targeting interferon-stimulated gene of 20 kDa protein (Isg20) inhibits ribosome biogenesis to ameliorate the progression of renal fibrosis.
title_fullStr Targeting interferon-stimulated gene of 20 kDa protein (Isg20) inhibits ribosome biogenesis to ameliorate the progression of renal fibrosis.
title_full_unstemmed Targeting interferon-stimulated gene of 20 kDa protein (Isg20) inhibits ribosome biogenesis to ameliorate the progression of renal fibrosis.
title_short Targeting interferon-stimulated gene of 20 kDa protein (Isg20) inhibits ribosome biogenesis to ameliorate the progression of renal fibrosis.
title_sort targeting interferon stimulated gene of 20 kda protein isg20 inhibits ribosome biogenesis to ameliorate the progression of renal fibrosis
url https://doi.org/10.1371/journal.pone.0322639
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