Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin

Abstract Neointimal hyperplasia is a pathological vascular remodeling caused by abnormal proliferation and migration of subintimal vascular smooth muscle cells (VSMCs) following intimal injury. There is increasing evidence that tRNA-derived small RNA (tsRNA) plays an important role in vascular remod...

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Main Authors: Qi-Lan Jiang, Jia-Ying Xu, Qing-Ping Yao, Rui Jiang, Qin Xu, Bo-Tao Zhang, Tao Li, Jun Jiang
Format: Article
Language:English
Published: BMC 2024-01-01
Series:Cellular & Molecular Biology Letters
Subjects:
Online Access:https://doi.org/10.1186/s11658-023-00523-z
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author Qi-Lan Jiang
Jia-Ying Xu
Qing-Ping Yao
Rui Jiang
Qin Xu
Bo-Tao Zhang
Tao Li
Jun Jiang
author_facet Qi-Lan Jiang
Jia-Ying Xu
Qing-Ping Yao
Rui Jiang
Qin Xu
Bo-Tao Zhang
Tao Li
Jun Jiang
author_sort Qi-Lan Jiang
collection DOAJ
description Abstract Neointimal hyperplasia is a pathological vascular remodeling caused by abnormal proliferation and migration of subintimal vascular smooth muscle cells (VSMCs) following intimal injury. There is increasing evidence that tRNA-derived small RNA (tsRNA) plays an important role in vascular remodeling. The purpose of this study is to search for tsRNAs signature of neointima formation and to explore their potential functions. The balloon injury model of rat common carotid artery was replicated to induce intimal hyperplasia, and the differentially expressed tsRNAs (DE-tsRNAs) in arteries with intimal hyperplasia were screened by small RNA sequencing and tsRNA library. A total of 24 DE-tsRNAs were found in the vessels with intimal hyperplasia by small RNA sequencing. In vitro, tRF-Glu-CTC inhibited the expression of fibromodulin (FMOD) in VSMCs, which is a negative modulator of TGF-β1 activity. tRF-Glu-CTC also increased VSMC proliferation and migration. In vivo experiments showed that inhibition of tRF-Glu-CTC expression after balloon injury of rat carotid artery can reduce the neointimal area. In conclusion, tRF-Glu-CTC expression is increased after vascular injury and inhibits FMOD expression in VSMCs, which influences neointima formation. On the other hand, reducing the expression of tRF-Glu-CTC after vascular injury may be a potential approach to prevent vascular stenosis.
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spelling doaj.art-ca6338f3bee14f67b6944fd2a1e2e8e12024-01-07T12:35:49ZengBMCCellular & Molecular Biology Letters1689-13922024-01-0129111910.1186/s11658-023-00523-zTransfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulinQi-Lan Jiang0Jia-Ying Xu1Qing-Ping Yao2Rui Jiang3Qin Xu4Bo-Tao Zhang5Tao Li6Jun Jiang7Department of Clinical Nutrition, Affiliated Hospital of Southwest Medical UniversityDepartment of General Surgery (Thyroid Surgery), The Affiliated Hospital of Southwest Medical UniversityInstitute of Mechanobiology and Medical Engineering, School of Life Science and Biotechnology, Shanghai Jiao Tong UniversityDepartment of Urology, Affiliated Hospital of Southwest Medical UniversityDepartment of General Surgery (Thyroid Surgery), The Affiliated Hospital of Southwest Medical UniversityDepartment of General Surgery (Thyroid Surgery), The Affiliated Hospital of Southwest Medical UniversityKey Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical UniversityDepartment of General Surgery (Thyroid Surgery), The Affiliated Hospital of Southwest Medical UniversityAbstract Neointimal hyperplasia is a pathological vascular remodeling caused by abnormal proliferation and migration of subintimal vascular smooth muscle cells (VSMCs) following intimal injury. There is increasing evidence that tRNA-derived small RNA (tsRNA) plays an important role in vascular remodeling. The purpose of this study is to search for tsRNAs signature of neointima formation and to explore their potential functions. The balloon injury model of rat common carotid artery was replicated to induce intimal hyperplasia, and the differentially expressed tsRNAs (DE-tsRNAs) in arteries with intimal hyperplasia were screened by small RNA sequencing and tsRNA library. A total of 24 DE-tsRNAs were found in the vessels with intimal hyperplasia by small RNA sequencing. In vitro, tRF-Glu-CTC inhibited the expression of fibromodulin (FMOD) in VSMCs, which is a negative modulator of TGF-β1 activity. tRF-Glu-CTC also increased VSMC proliferation and migration. In vivo experiments showed that inhibition of tRF-Glu-CTC expression after balloon injury of rat carotid artery can reduce the neointimal area. In conclusion, tRF-Glu-CTC expression is increased after vascular injury and inhibits FMOD expression in VSMCs, which influences neointima formation. On the other hand, reducing the expression of tRF-Glu-CTC after vascular injury may be a potential approach to prevent vascular stenosis.https://doi.org/10.1186/s11658-023-00523-zTransfer RNA (tRNA)-derived small RNAs (tsRNAs)Vascular smooth muscle cellVascular remodelingNeointimal hyperplasia (NIH)ProliferationMigration
spellingShingle Qi-Lan Jiang
Jia-Ying Xu
Qing-Ping Yao
Rui Jiang
Qin Xu
Bo-Tao Zhang
Tao Li
Jun Jiang
Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin
Cellular & Molecular Biology Letters
Transfer RNA (tRNA)-derived small RNAs (tsRNAs)
Vascular smooth muscle cell
Vascular remodeling
Neointimal hyperplasia (NIH)
Proliferation
Migration
title Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin
title_full Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin
title_fullStr Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin
title_full_unstemmed Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin
title_short Transfer RNA-derived small RNA tRF-Glu-CTC attenuates neointimal formation via inhibition of fibromodulin
title_sort transfer rna derived small rna trf glu ctc attenuates neointimal formation via inhibition of fibromodulin
topic Transfer RNA (tRNA)-derived small RNAs (tsRNAs)
Vascular smooth muscle cell
Vascular remodeling
Neointimal hyperplasia (NIH)
Proliferation
Migration
url https://doi.org/10.1186/s11658-023-00523-z
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