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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2021
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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) |
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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 |
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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 |
work_keys_str_mv |
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