title: Down-regulated Six2 by knockdown of neurofibromin results in apoptosis of metanephric mesenchyme cells in vitro.
abstract: Embryonic Six2-positive nephron progenitor cells adjacent to ureteric bud tips ultimately give rise to nephron structures, including proximal and distal tubules, podocytes, Bowman's capsules, and the glomeruli. This process requires an internal balance between self-renew and differentiation of the nephron progenitor cells, which is mediated by numerous molecules. Recent studies have shown that the neurofibromin (Nf1) null mutant mouse embryos have an 18- to 24-h developmental delay in metanephros manifesting retardation in its cephalad repositioning and reduction number of glomeruli. However, the underlying inter-/intracellular signaling mechanisms responsible for reducing number of glomeruli during nephrogenesis remain to be fully elucidated. Here, we originally detected the Nf1 expression in developing kidney and metanephric mesenchyme cells. Surprisingly, Nf1 knockdown by small interfering RNAs in the metanephric mesenchyme cells (mK3) resulted in a decreased expression of Six2, the key marker of renal progenitor cells, while the ratio of apoptotic cells was significantly increased. Furthermore, overexpression of Six2 in mk3 cells partially rescued apoptosis phenotype. Collectively, these results implied that knockdown of Nf1 resulted in apoptosis of mK3 cells in vitro probably through down-regulation of Six2 expression. Collectively, we demonstrated that down-regulated Six2 by knockdown of Nf1 resulted in apoptosis of mK3 cells in vitro. These results implied that inhibition of Nf1 may delay metanephros development via down-regulation of Six2.
authors.affiliation: The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory Medicine, Chongqing Medical University, 1# Yixueyuan Road, Yuzhong District, 400016, Chongqing, People's Republic of China.
authors.forename: Puhui
authors.initials: P
authors.lastname: Zhou
authors.forename: Tielin
authors.initials: T
authors.lastname: Chen
authors.forename: Yin
authors.initials: Y
authors.lastname: Fang
authors.forename: Honglian
authors.initials: H
authors.lastname: Wang
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Ma
authors.forename: Lu
authors.initials: L
authors.lastname: He
authors.forename: Qianyin
authors.initials: Q
authors.lastname: Li
authors.forename: Tianming
authors.initials: T
authors.lastname: Liu
authors.forename: Xianggui
authors.initials: X
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Nie
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Yuan
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Rui
authors.initials: R
authors.lastname: Peng
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D007668:Kidney / Q000166:cytology / Q000254:growth & development*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009399:Nephrons / Q000196:embryology*; D025542:Neurofibromin 1 / Q000235:genetics* / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D025542:Neurofibromin 1; C497420:Six2 protein, mouse; D014157:Transcription Factors