| Project/Area Number |
17591358
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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 |
General surgery
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| Research Institution | Fujita Health University |
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Principal Investigator |
HIBI Yatsuka Fujita Health University, School of Medicine, Senior lecturer (10399024)
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| Co-Investigator(Kenkyū-buntansha) |
IWASE Katsumi Fujita Health University, School of Medicine, professor (70148261)
IMAI Tsuneo Nagoya University, School of Medicine, Senior lecture (80252245)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | parathyroid / chronic renal failure / protein kinase A |
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| Research Abstract |
In this study, we tried to identify the genes that are upregulated in NH.The cDNA population prepared from DH was subtracted from that from NH by a PCR-based cDNA subtraction method. The resultant cDNAs were cloned and sequenced. One of the nuclear genes identified was PRKAR1A gene, which encodes type Iα regulatory subunit (RIα) of cAMP-dependent protein kinase (PKA). Immunohistochemical analysis demonstrated that Riα was abundantly expressed in the nodular region, whereas the adjacent diffuse region displayed a relatively low expression. Northern and Western blot analyses demonstrated the upregulation of Riα expression in most of NH tested. Determination of PKA activities revealed that free PKA activities measured in the absence of cAMP in the assay were inversely correlated with the Riα expression, indicating the functional significance of Riα. Upregulation. These results suggest that the aberrant expression of Riα is involved in the diffuse-to-nodular transformation of hyperplasia of parathyroid glands, by impairing cAMP/PKA signal transduction. Moreover we carried out to determine whether PRKAR1α also overexpresses in adenomas of primary hyperparathyroidism (PHP) that is considered to proliferate monoclonally as well as nodular hyperplasia in renal hyperparathyroidism. Western blot analysis, Immunohistochemical analysis revealed upregulation of Riα in adenoma. The result of PKA activity assay in adenomas of primary hyperparathyroidism was same as in nodular hyperplasias in renal hyperparathyroidism. PCNA immunohistochemical staining was performed to evaluate whether Rlα positive cells are proliferative. PCNA positive cells were mainly included in oxyphilic cells of adenoma where Rlα were strongly expressed. Whereas, there was no significantly difference in PK Ac expression between oxyphilic cells and chief cells. These findings indicated that AMP/PKA signaling inactivation via Riα may stimulates the proliferation of parathyroid cell in hyperparathyroidism.
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