Molecular and Cellular Biochemistry

, Volume 390, Issue 1, pp 205–213

Down-regulated Six2 by knockdown of neurofibromin results in apoptosis of metanephric mesenchyme cells in vitro

Authors

  • Puhui Zhou
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
  • Tielin Chen
    • Core Facility of Gene Engineered Mice, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University
  • Yin Fang
    • Core Facility of Gene Engineered Mice, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University
  • Honglian Wang
    • Core Facility of Gene Engineered Mice, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University
  • Mi Li
    • Core Facility of Gene Engineered Mice, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University
  • Pengpeng Ma
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
  • Lu He
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
  • Qianyin Li
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
  • Tianming Liu
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
  • Xianggui Yang
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
  • Fang Nie
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
  • Xiaoyan Wang
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
  • Yue Yuan
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
  • Li Zhou
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
  • Rui Peng
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
  • Zhicheng Liu
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
    • The Institute of Molecular Nephrology and the Creative Training Center for Undergraduates, the College of Laboratory MedicineChongqing Medical University
    • Core Facility of Gene Engineered Mice, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University
    • The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory MedicineChongqing Medical University
Article

DOI: 10.1007/s11010-014-1971-0

Cite this article as:
Zhou, P., Chen, T., Fang, Y. et al. Mol Cell Biochem (2014) 390: 205. doi:10.1007/s11010-014-1971-0

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.

Keywords

Nf1Six2Cell apoptosisMetanephric mesenchyme

Copyright information

© Springer Science+Business Media New York 2014