1999 Fiscal Year Final Research Report Summary
The clinical analysis of the pathophysiological significance in the kidney disease of the new bioactivation molecule.
| Project/Area Number |
10671012
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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 | Tokyo Women's Medical College |
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Principal Investigator |
ITO Katumi Tokyo Women's Medical University, Dept. of Pediatric Nephrology, School of Medicine Professor, 医学部, 教授 (90056771)
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| Co-Investigator(Kenkyū-buntansha) |
AKIOKA Yuko Tokyo Women's Medical University, Dept. of Pediatric Nephrology, School of Medicine Instructor, 医学部, 助手 (90212422)
SHIRAGA Hiroshi Tokyo Women's Medical University, Dept. of Pediatric Nephrology, School of Medicine Associate Professor, 医学部, 助教授 (60175396)
YOSHIOKA Toshomasa Tokyo Women's Medical University, Dept. of Pediatric Nephrology, School of Medicine Associate Professor, 医学部, 助教授 (60146438)
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| Project Period (FY) |
1998 – 1999
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| Keywords | AcSDKP / thymocin β4 / proliferation / anqiotensin converting enzyme / RT-PCR / interstitial fibroblasts / Captopril / renal diseases |
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| Research Abstract |
N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) was recently demonstrated as an inhibitory factor of hematopoiesis. The precursor of AcSDKP, thymocin β4, is expressed in many tissues including kidney, therefore, AcSDKP is suggested to be produced in those tissues. AcSDKP is specifically degraded by the N-terminal active site of angiotensin converting enzyme (ACE). Since no previous study addressed the biological effects of AcSDKP on renal cells, the present study examined the antiproliferative effect of AcSDKP and the molecular interaction of ACEI and AcSDKP in renal cells, namely, interstitial fibroblasts (IFB).
Spectrophotometric measurements of alamar blue oxidation was used as an index of proliferation. An addition of AcSDKP (10-ィイD1-9ィエD1 to 10-ィイD1-5ィエD1 M ) for 48 hours in IFB culuted in medium with 4% fetal bovine serum or with 1 μM phorbol ester resulted in a concentration-dependent attenuation in the proliferation rate (significant difference to non-treated cells at 10ィイD1-7ィエD1 to 10ィイD1-5ィエD1 M AcSDKP). While individual treatment with 100 nM captopril or 10ィイD1-8ィエD1 M AcSDKP did not alter the rate of proliferation, the combined treatment significantly reduced the proliferation. Such synergism was not demonstrated in the combination with lisinopril and AcSDKP. In these experimental conditions, no change in mRNA expressions of thymocin β4 and ACE was demonstrated by the RT-PCR.
Thus, AcSDKP attenuated the proliferation of renal cells. Not Lisinopril but Captopril which blocks N-terminal active site of ACE, enhanced the biological effect of AcSDKP. Thus, AcSDKP may be an endogenous modulator of renal cell proliferation, and antiproliferative action of some ACEI in renal diseases may be partly mediated by AcSDKP.
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