2011 Fiscal Year Final Research Report
Mechanism of regeneration of renal tubular cells and differentiation from ES and iPS cells to renal tubular cells
| Project/Area Number |
21591038
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Keywords | 腎臓 / 尿細管 / 再生医学 / ES細胞 / iPS細胞 |
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| Research Abstract |
The S3 segment of the kidney proximal tubule is highly susceptible to ischemia insults but has a remarkable capacity to repair its structure and function. By applying the "toxin receptor mediated cell knockout" method under the control of the S3 segment-specific promoter Gsl5, we established a transgenic mouse line expressing the human diphtheria toxin(DT) receptor only in the S3 segment. The administration of DT to these transgenic mice caused the selective ablation of S3 segment cells in a dose-dependent manner. These results indicate that this transgenic mouse can suffer acute kidney injury(AKI) caused by S3 segment-specific damage after DT administration. This transgenic line offers an excellent model to uncover the mechanisms of AKI and its rapid recovery.
We tried to establish differentiation method of ES cells and iPS cells into renal tubular cells. In ES cells, Activin enhanced the differentiation of ES cells to tubular cells, judging by expression of Ksp-Cadherin, the epithelial marker. Activin also enhanced the differentiation of iPS cells to tubular cells, although the enhancement was lower than in ES cells. We generated monoclonal antibody against the extracellular domain of Ksp-Cadherin. Flow cytometry using the antibody purified the Ksp-positive cells, which formed tubular structure on Matrigel. We established the differentiation method of ES and iPS cells into renal tubular cells.
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[Journal Article] Selective depletion of mouse kidney proximal straight tubule cells causes acute kidney injury2012
Author(s)
Sekine M, Monkawa T, Morizane R, Matsuoka K, Taya C, Akita Y, Joh K, Itoh H, Hayashi M, Kikkawa Y, Kohno K, Suzuki A, Yonekawa H.
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Journal Title
Transgenic Res
Volume: 21
Pages: 51-62
Peer Reviewed
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