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Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model

The global burden of chronic kidney disease is increasing, and the majority of these diseases are progressive. Special site-targeted drugs are emerging as alternatives to traditional drugs. Oligonucleotides (ODNs) have been proposed as effective therapeutic tools in specific molecular target therapi...

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Autores principales: Kim, Young-Ah, Gu, Hyemin, Gwon, Mi-Gyeong, An, Hyun-Jin, Bae, Seongjae, Leem, Jaechan, Jung, Hyun Jin, Park, Kwan-Kyu, Lee, Sun-Jae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569483/
https://www.ncbi.nlm.nih.gov/pubmed/36232665
http://dx.doi.org/10.3390/ijms231911365
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author Kim, Young-Ah
Gu, Hyemin
Gwon, Mi-Gyeong
An, Hyun-Jin
Bae, Seongjae
Leem, Jaechan
Jung, Hyun Jin
Park, Kwan-Kyu
Lee, Sun-Jae
author_facet Kim, Young-Ah
Gu, Hyemin
Gwon, Mi-Gyeong
An, Hyun-Jin
Bae, Seongjae
Leem, Jaechan
Jung, Hyun Jin
Park, Kwan-Kyu
Lee, Sun-Jae
author_sort Kim, Young-Ah
collection PubMed
description The global burden of chronic kidney disease is increasing, and the majority of these diseases are progressive. Special site-targeted drugs are emerging as alternatives to traditional drugs. Oligonucleotides (ODNs) have been proposed as effective therapeutic tools in specific molecular target therapies for several diseases. We designed ring-type non-coding RNAs (ncRNAs), also called mTOR ODNs to suppress mammalian target rapamycin (mTOR) translation. mTOR signaling is associated with excessive cell proliferation and fibrogenesis. In this study, we examined the effects of mTOR suppression on chronic renal injury. To explore the regulation of fibrosis and inflammation in unilateral ureteral obstruction (UUO)-induced injury, we injected synthesized ODNs via the tail vein of mice. The expression of inflammatory-related markers (interleukin-1β, tumor necrosis factor-α), and that of fibrosis (α-smooth muscle actin, fibronectin), was decreased by synthetic ODNs. Additionally, ODN administration inhibited the expression of autophagy-related markers, microtubule-associated protein light chain 3, Beclin1, and autophagy-related gene 5-12. We confirmed that ring-type ODNs inhibited fibrosis, inflammation, and autophagy in a UUO mouse model. These results suggest that mTOR may be involved in the regulation of autophagy and fibrosis and that regulating mTOR signaling may be a therapeutic strategy against chronic renal injury.
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spelling pubmed-95694832022-10-17 Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model Kim, Young-Ah Gu, Hyemin Gwon, Mi-Gyeong An, Hyun-Jin Bae, Seongjae Leem, Jaechan Jung, Hyun Jin Park, Kwan-Kyu Lee, Sun-Jae Int J Mol Sci Article The global burden of chronic kidney disease is increasing, and the majority of these diseases are progressive. Special site-targeted drugs are emerging as alternatives to traditional drugs. Oligonucleotides (ODNs) have been proposed as effective therapeutic tools in specific molecular target therapies for several diseases. We designed ring-type non-coding RNAs (ncRNAs), also called mTOR ODNs to suppress mammalian target rapamycin (mTOR) translation. mTOR signaling is associated with excessive cell proliferation and fibrogenesis. In this study, we examined the effects of mTOR suppression on chronic renal injury. To explore the regulation of fibrosis and inflammation in unilateral ureteral obstruction (UUO)-induced injury, we injected synthesized ODNs via the tail vein of mice. The expression of inflammatory-related markers (interleukin-1β, tumor necrosis factor-α), and that of fibrosis (α-smooth muscle actin, fibronectin), was decreased by synthetic ODNs. Additionally, ODN administration inhibited the expression of autophagy-related markers, microtubule-associated protein light chain 3, Beclin1, and autophagy-related gene 5-12. We confirmed that ring-type ODNs inhibited fibrosis, inflammation, and autophagy in a UUO mouse model. These results suggest that mTOR may be involved in the regulation of autophagy and fibrosis and that regulating mTOR signaling may be a therapeutic strategy against chronic renal injury. MDPI 2022-09-26 /pmc/articles/PMC9569483/ /pubmed/36232665 http://dx.doi.org/10.3390/ijms231911365 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Young-Ah
Gu, Hyemin
Gwon, Mi-Gyeong
An, Hyun-Jin
Bae, Seongjae
Leem, Jaechan
Jung, Hyun Jin
Park, Kwan-Kyu
Lee, Sun-Jae
Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model
title Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model
title_full Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model
title_fullStr Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model
title_full_unstemmed Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model
title_short Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model
title_sort synthetic non-coding rna for suppressing mtor translation to prevent renal fibrosis related to autophagy in uuo mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569483/
https://www.ncbi.nlm.nih.gov/pubmed/36232665
http://dx.doi.org/10.3390/ijms231911365
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