Overexpression of long noncoding RNA 4933425B07Rik leads to renal hypoplasia by inactivating Wnt/β-catenin signaling pathway

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Lihong Tan¹  Minghui Yu²  Chunyan Wang²  Shanshan Xue²  Qian Shen²  Yaxin Li²  Hong Xu²  Haixin Ju²  Xuanjin Du²  Jialu Liu²  Xiaohui Wu³ 

[1] Department of Nephrology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China;Department of Nephrology, Children’s Hospital of Fudan University, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China;Department of Nephrology, Children’s Hospital of Fudan University, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China;State 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, China;

关键词: PB transposon;    lncRNAs;    4933425B07Rik;    CAKUT;    renal development;    Wnt/β-catenin signaling pathway;   

DOI  :  10.3389/fcell.2023.1267440

 received in 2023-08-10, accepted in 2023-10-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

Congenital anomalies of the kidney and urinary tract (CAKUT) is a general term for a class of diseases that are mostly caused by intrauterine genetic development limitation. Without timely intervention, certain children with CAKUT may experience progressive decompensation and a rapid decline in renal function, which will ultimately result in end-stage renal disease. At present, a comprehensive understanding of the pathogenic signaling events of CAKUT is lacking. The role of long noncoding RNAs (lncRNAs) in renal development and disease have recently received much interest. In previous research, we discovered that mice overexpressing the lncRNA 4933425B07Rik (Rik) showed a range of CAKUT phenotypes, primarily renal hypoplasia. The current study investigated the molecular basis of renal hypoplasia caused by Rik overexpression. We first used Rapid Amplification of cDNA ends (RACE) to obtain the full-length sequence of Rik in Rik+/+;Hoxb7 mice. Mouse proximal renal tubule epithelial cells (MPTCs) line with Rik overexpression was constructed using lentiviral methods, and mouse metanephric mesenchyme cell line (MK3) with Rik knockout was then constructed by the CRISPR‒Cas9 method. We performed RNA-seq on the Rik-overexpressing cell line to explore possible differentially expressed molecules and pathways. mRNA expression was confirmed by qRT‒PCR. Reduced levels of Wnt10b, Fzd8, and β-catenin were observed when Rik was expressed robustly. On the other hand, these genes were more highly expressed when Rik was knocked out. These results imply that overabundance of Rik might inhibit the Wnt/β-catenin signaling pathway, which may result in renal hypoplasia. In general, such research might help shed light on CAKUT causes and processes and offer guidance for creating new prophylactic and therapeutic strategies.

【 授权许可】

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Copyright © 2023 Xue, Du, Yu, Ju, Tan, Li, Liu, Wang, Wu, Xu and Shen.