Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7

Introduction: Transforming growth factor-β (TGF-β), a common outcome of various progressive chronic kidney diseases, can regulate and induce fibrosis. Objective: The study aimed to identify downstream targets of lncRNA ENST00000453774.1 (lnc453774.1) and outline their functions on the development of...

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Autores principales: Xiangning Yuan, Wen-bin Tang, Ling Peng, Yusa Chen, Shumei Tang, Huipeng Ge, Xiufen Wang, Xiangcheng Xiao
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Publicado: Karger Publishers 2021
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spelling oai:doaj.org-article:0845dde470144c9592a4a43dfd5ed87e2021-11-04T14:40:31ZElevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF71420-40961423-014310.1159/000515624https://doaj.org/article/0845dde470144c9592a4a43dfd5ed87e2021-10-01T00:00:00Zhttps://www.karger.com/Article/FullText/515624https://doaj.org/toc/1420-4096https://doaj.org/toc/1423-0143Introduction: Transforming growth factor-β (TGF-β), a common outcome of various progressive chronic kidney diseases, can regulate and induce fibrosis. Objective: The study aimed to identify downstream targets of lncRNA ENST00000453774.1 (lnc453774.1) and outline their functions on the development of renal fibrosis. Methods: HK-2 cells were induced with 5 ng/mL TGF-β1 for 24 h to construct a renal fibrosis cell model. Differentially expressed genes (DEGs) targeted by lnc453774.1 in TGF-β1-induced renal fibrosis were identified using RNA sequencing. The dataset GSE23338 was employed to identify DEGs in 48-h TGF-β1-stimulated human kidney epithelial cells, and these DEGs were intersected with genes in the key module using weighted gene co-expression network analysis to generate key genes associated with renal fibrosis. MicroRNAs (miRs) that had targeting relationship with keys genes and lnc453774.1 were predicted by using Miranda software, and important genes were intersected with key genes that had targeting relationship with these miRs. Key target genes by lnc453774.1 were identified in a protein-protein interaction network among lnc453774.1, important genes, and reported genes related to autophagy, oxidative stress, and cell adhesion. Results: Key genes in the key module (turquoise) were intersected with DEGs in the dataset GSE23338 and yielded 20 key genes regulated by lnc453774.1 involved in renal fibrosis. Fourteen miRs had targeting relationship with lnc453774.1 and key genes, and 8 important genes targeted by these 14 miRs were identified. Fibrillin-1 (FBN1), insulin-like growth factor 1 receptor (IGF1R), and Kruppel-like factor 7 (KLF7) were identified to be involved in autophagy, oxidative stress, and cell adhesion and were elevated in the lnc453774.1-overexpressing TGF-β1-induced cells. Conclusion: These results show FBN1, IGF1R, and KLF7 serve as downstream targets of lnc453774.1, and that lnc453774.1 may protect against renal fibrosis through competing endogenous miRs which target FBN1, IGF1R, and KLF7 mRNAs.Xiangning YuanWen-bin TangLing PengYusa ChenShumei TangHuipeng GeXiufen WangXiangcheng XiaoKarger Publishersarticlerenal fibrosislong noncoding rna enst00000453774.1transforming growth factor-β1weighted gene correlation network analysisrna sequencingDermatologyRL1-803Diseases of the circulatory (Cardiovascular) systemRC666-701Diseases of the genitourinary system. UrologyRC870-923ENKidney & Blood Pressure Research, Vol 46, Iss 5, Pp 563-573 (2021)
institution DOAJ
collection DOAJ
language EN
topic renal fibrosis
long noncoding rna enst00000453774.1
transforming growth factor-β1
weighted gene correlation network analysis
rna sequencing
Dermatology
RL1-803
Diseases of the circulatory (Cardiovascular) system
RC666-701
Diseases of the genitourinary system. Urology
RC870-923
spellingShingle renal fibrosis
long noncoding rna enst00000453774.1
transforming growth factor-β1
weighted gene correlation network analysis
rna sequencing
Dermatology
RL1-803
Diseases of the circulatory (Cardiovascular) system
RC666-701
Diseases of the genitourinary system. Urology
RC870-923
Xiangning Yuan
Wen-bin Tang
Ling Peng
Yusa Chen
Shumei Tang
Huipeng Ge
Xiufen Wang
Xiangcheng Xiao
Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7
description Introduction: Transforming growth factor-β (TGF-β), a common outcome of various progressive chronic kidney diseases, can regulate and induce fibrosis. Objective: The study aimed to identify downstream targets of lncRNA ENST00000453774.1 (lnc453774.1) and outline their functions on the development of renal fibrosis. Methods: HK-2 cells were induced with 5 ng/mL TGF-β1 for 24 h to construct a renal fibrosis cell model. Differentially expressed genes (DEGs) targeted by lnc453774.1 in TGF-β1-induced renal fibrosis were identified using RNA sequencing. The dataset GSE23338 was employed to identify DEGs in 48-h TGF-β1-stimulated human kidney epithelial cells, and these DEGs were intersected with genes in the key module using weighted gene co-expression network analysis to generate key genes associated with renal fibrosis. MicroRNAs (miRs) that had targeting relationship with keys genes and lnc453774.1 were predicted by using Miranda software, and important genes were intersected with key genes that had targeting relationship with these miRs. Key target genes by lnc453774.1 were identified in a protein-protein interaction network among lnc453774.1, important genes, and reported genes related to autophagy, oxidative stress, and cell adhesion. Results: Key genes in the key module (turquoise) were intersected with DEGs in the dataset GSE23338 and yielded 20 key genes regulated by lnc453774.1 involved in renal fibrosis. Fourteen miRs had targeting relationship with lnc453774.1 and key genes, and 8 important genes targeted by these 14 miRs were identified. Fibrillin-1 (FBN1), insulin-like growth factor 1 receptor (IGF1R), and Kruppel-like factor 7 (KLF7) were identified to be involved in autophagy, oxidative stress, and cell adhesion and were elevated in the lnc453774.1-overexpressing TGF-β1-induced cells. Conclusion: These results show FBN1, IGF1R, and KLF7 serve as downstream targets of lnc453774.1, and that lnc453774.1 may protect against renal fibrosis through competing endogenous miRs which target FBN1, IGF1R, and KLF7 mRNAs.
format article
author Xiangning Yuan
Wen-bin Tang
Ling Peng
Yusa Chen
Shumei Tang
Huipeng Ge
Xiufen Wang
Xiangcheng Xiao
author_facet Xiangning Yuan
Wen-bin Tang
Ling Peng
Yusa Chen
Shumei Tang
Huipeng Ge
Xiufen Wang
Xiangcheng Xiao
author_sort Xiangning Yuan
title Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7
title_short Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7
title_full Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7
title_fullStr Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7
title_full_unstemmed Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7
title_sort elevation of lncrna enst00000453774.1 prevents renal fibrosis by upregulating fbn1, igf1r, and klf7
publisher Karger Publishers
publishDate 2021
url https://doaj.org/article/0845dde470144c9592a4a43dfd5ed87e
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