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Regeneration of sclerosed glomeruli : Mechanism of dedifferentiation and phenotypic changes in podocytes and induce redifferentiation.

Research Project

Project/Area Number 17590818
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionUniversity of Tsukuba

Principal Investigator

NAGATA Michio  University of Tsukuba, Graduate School of Comprehensive Human Sciences, Molecular Pathology, Professor, 大学院人間総合科学研究科, 教授 (10192238)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordskidney / glomerulosclerosis / podocyte / differentiation / phenotype / glomerulonephritis / nestin / regeneration / トランスジェニックマウス / ROSAマウス / nephrin-Cre / 抗基底膜抗体腎炎 / 上皮脱分化
Research Abstract

To monitor podocytes derived cells in the pathologic process of glomerular disease, we generate Nephrin-Cre/Rosa26 mice and then we crossed them with p21 deficient mice and induced anti-glomerular antibody glomerulonephritis. The kidney showed marked proteinuria coupled with glomerular epithelial hyperplasia. To analyze the origin and phenotype of these cells, immunohistochemistry for several podocytes markers and incorporation of BrdU was analyzed. Hypercellular lesions were virtually both LacZ and WT1 negative. In addition, we did not find out for LacZ+/WT1-cells or LacZ+/synaptopodin-cells. Thus podocytes dedifferentiation is not occurring in this setting of experimental glomerulonephritis.
We are now investigating the plasticity of podocytes focusing on the function of nestin intermediate filament, neurogenic progenitor marker, we found nestin is predominantly expressed in the differentiated podocytes and cytoplasmic distribution of nestin is different from that of actin.siRNA of nestin for immortalized podocytes cell line reveals suppression of process formation suggesting nestin function for podocytes plasticity.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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