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

作者全名："Xue, Shanshan; Du, Xuanjin; Yu, Minghui; Ju, Haixin; Tan, Lihong; Li, Yaxin; Liu, Jialu; Wang, Chunyan; Wu, Xiaohui; Xu, Hong; Shen, Qian"

作者地址："[Xue, Shanshan; Du, Xuanjin; Yu, Minghui; Ju, Haixin; Li, Yaxin; Liu, Jialu; Wang, Chunyan; Wu, Xiaohui; Xu, Hong; Shen, Qian] Fudan Univ, Childrens Hosp, Shanghai Kidney Dev & Pediat Kidney Dis Res Ctr, Dept Nephrol, Shanghai, Peoples R China; [Tan, Lihong] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Dept Nephrol,Minist Educ,Key Lab Child Dev & Disor, Chongqing, Peoples R China; [Wu, Xiaohui] Fudan Univ, State Key Lab Genet Engn, Shanghai, Peoples R China; [Wu, Xiaohui] Fudan Univ, Inst Dev Biol & Mol Med, Natl Ctr Int Res Dev & Dis, Sch Life Sci,Collaborat Innovat Ctr Genet & Dev, Shanghai, Peoples R China"

通信作者："Xu, H; Shen, Q (通讯作者)，Fudan Univ, Childrens Hosp, Shanghai Kidney Dev & Pediat Kidney Dis Res Ctr, Dept Nephrol, Shanghai, Peoples R China."

来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001093402500001

JCR分区：Q1

影响因子：4.6

年份：2023

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

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

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 beta-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/beta-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."

基金机构："National Key Research and Development Program of China [2021YFC2701001]; National Natural Science Foundation of China [82070686, 8190032071]; Shanghai Science and Technology Commission Western Medicine Guidance Project [20ZR1408700]; Establishment, Performance, and Quality Control of the Standardized Phenotype Analysis Process Grant [2018YFA0801102]"

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Key Research and Development Program of China (2021YFC2701001); the National Natural Science Foundation of China (82070686 and 8190032071); the Shanghai Science and Technology Commission Western Medicine Guidance Project (20ZR1408700); and the Establishment, Performance, and Quality Control of the Standardized Phenotype Analysis Process Grant (2018YFA0801102)."