Overexpression of Long Non-coding RNA 4933425B07Rik Causes Urinary Malformations in Mice
Congenital anomalies of the kidney and urinary tract (CAKUT) is a common birth defect and is the leading cause of end-stage renal disease in children. The etiology of CAKUT is complex and includes mainly genetic and environmental factors. However, these factors cannot fully explain the etiological m...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.594640/full |
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| author | Lihong Tan Minghui Yu Yaxin Li Shanshan Xue Jing Chen Yihui Zhai Xiaoyan Fang Jialu Liu Jiaojiao Liu Xiaohui Wu Xiaohui Wu Hong Xu Qian Shen |
| author_facet | Lihong Tan Minghui Yu Yaxin Li Shanshan Xue Jing Chen Yihui Zhai Xiaoyan Fang Jialu Liu Jiaojiao Liu Xiaohui Wu Xiaohui Wu Hong Xu Qian Shen |
| author_sort | Lihong Tan |
| collection | DOAJ |
| description | Congenital anomalies of the kidney and urinary tract (CAKUT) is a common birth defect and is the leading cause of end-stage renal disease in children. The etiology of CAKUT is complex and includes mainly genetic and environmental factors. However, these factors cannot fully explain the etiological mechanism of CAKUT. Recently, participation of long non-coding RNAs (lncRNAs) in the development of the circulatory and nervous systems was demonstrated; however, the role of lncRNAs in the development of the kidney and urinary tract system is unclear. In this study, we used the piggyBac (PB) transposon-based mutagenesis to construct a mouse with lncRNA 4933425B07Rik (Rik) PB insertion (RikPB/PB) and detected overexpression of Rik and a variety of developmental abnormalities in the urinary system after PB insertion, mainly including renal hypo/dysplasia. The number of ureteric bud (UB) branches in the RikPB/PB embryonic kidney was significantly decreased in embryonic kidney culture. Only bone morphogenetic protein 4 (Bmp4), a key molecule regulating UB branching, is significantly downregulated in RikPB/PB embryonic kidney, while the expression levels of other molecules involved in the regulation of UB branching were not significantly different according to the RNA-sequencing (RNA-seq) data, and the results were verified by quantitative real-time polymerase chain reaction (RT-PCR) and immunofluorescence assays. Besides, the expression of pSmad1/5/8, a downstream molecule of BMP4 signaling, decreased by immunofluorescence. These findings suggest that abnormal expression of Rik may cause a reduction in the UB branches by reducing the expression levels of the UB branching-related molecule Bmp4, thus leading to the development of CAKUT. |
| first_indexed | 2024-12-20T08:44:42Z |
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| id | doaj.art-96afa664dcdb45b086d8ddc021475202 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-20T08:44:42Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-96afa664dcdb45b086d8ddc0214752022022-12-21T19:46:17ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.594640594640Overexpression of Long Non-coding RNA 4933425B07Rik Causes Urinary Malformations in MiceLihong Tan0Minghui Yu1Yaxin Li2Shanshan Xue3Jing Chen4Yihui Zhai5Xiaoyan Fang6Jialu Liu7Jiaojiao Liu8Xiaohui Wu9Xiaohui Wu10Hong Xu11Qian Shen12Department of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Children’s Hospital of Fudan University, Shanghai, ChinaCongenital anomalies of the kidney and urinary tract (CAKUT) is a common birth defect and is the leading cause of end-stage renal disease in children. The etiology of CAKUT is complex and includes mainly genetic and environmental factors. However, these factors cannot fully explain the etiological mechanism of CAKUT. Recently, participation of long non-coding RNAs (lncRNAs) in the development of the circulatory and nervous systems was demonstrated; however, the role of lncRNAs in the development of the kidney and urinary tract system is unclear. In this study, we used the piggyBac (PB) transposon-based mutagenesis to construct a mouse with lncRNA 4933425B07Rik (Rik) PB insertion (RikPB/PB) and detected overexpression of Rik and a variety of developmental abnormalities in the urinary system after PB insertion, mainly including renal hypo/dysplasia. The number of ureteric bud (UB) branches in the RikPB/PB embryonic kidney was significantly decreased in embryonic kidney culture. Only bone morphogenetic protein 4 (Bmp4), a key molecule regulating UB branching, is significantly downregulated in RikPB/PB embryonic kidney, while the expression levels of other molecules involved in the regulation of UB branching were not significantly different according to the RNA-sequencing (RNA-seq) data, and the results were verified by quantitative real-time polymerase chain reaction (RT-PCR) and immunofluorescence assays. Besides, the expression of pSmad1/5/8, a downstream molecule of BMP4 signaling, decreased by immunofluorescence. These findings suggest that abnormal expression of Rik may cause a reduction in the UB branches by reducing the expression levels of the UB branching-related molecule Bmp4, thus leading to the development of CAKUT.https://www.frontiersin.org/articles/10.3389/fcell.2021.594640/fulllong non-coding RNA4933425B07Rikcongenital anomalies of the kidney and urinary tractkidney developmentBmp4 |
| spellingShingle | Lihong Tan Minghui Yu Yaxin Li Shanshan Xue Jing Chen Yihui Zhai Xiaoyan Fang Jialu Liu Jiaojiao Liu Xiaohui Wu Xiaohui Wu Hong Xu Qian Shen Overexpression of Long Non-coding RNA 4933425B07Rik Causes Urinary Malformations in Mice Frontiers in Cell and Developmental Biology long non-coding RNA 4933425B07Rik congenital anomalies of the kidney and urinary tract kidney development Bmp4 |
| title | Overexpression of Long Non-coding RNA 4933425B07Rik Causes Urinary Malformations in Mice |
| title_full | Overexpression of Long Non-coding RNA 4933425B07Rik Causes Urinary Malformations in Mice |
| title_fullStr | Overexpression of Long Non-coding RNA 4933425B07Rik Causes Urinary Malformations in Mice |
| title_full_unstemmed | Overexpression of Long Non-coding RNA 4933425B07Rik Causes Urinary Malformations in Mice |
| title_short | Overexpression of Long Non-coding RNA 4933425B07Rik Causes Urinary Malformations in Mice |
| title_sort | overexpression of long non coding rna 4933425b07rik causes urinary malformations in mice |
| topic | long non-coding RNA 4933425B07Rik congenital anomalies of the kidney and urinary tract kidney development Bmp4 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.594640/full |
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