2018 Fiscal Year Final Research Report
Elucidation of the adrenal gland regeneration mechanism and application to adrenocortical autotransplantation
| Project/Area Number |
16K10483
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Kansai Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松田 公志 関西医科大学, 医学部, 教授 (20192338)
田中 進 関西医科大学, 医学部, 准教授 (30399472)
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| Research Collaborator |
TAKIZAWA Nae
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 副腎 / 自家移植 / 再生 / DHH / GLI1 |
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| Outline of Final Research Achievements |
Bilateral adrenalectomy forces the patient to undergo glucocorticoid replacement therapy and face a lifetime risk of adrenal crisis. Adrenal autotransplantation is considered useful to avoid adrenal crisis and the replacement therapy. However, the basic process of regeneration in adrenal autografts is poorly understood. Here, we investigated the essential regeneration factors in rat adrenocortical autografts, with a focus on the factors involved in adrenal development and steroidogenesis, such as Hh signalling. The autografts showed increased Dhh expressions 3 weeks after autotransplantation, but not Shh, which is the only Hh family member to have been reported to be expressed in the adrenal gland. Increased Gli1 expression was also found in the regenerated capsule 3 weeks after autotransplantation. Dhh and Gli1 might function in cooperation to regenerate adrenocortical autografts. This is the first report to clearly show Dhh expression and its elevation in the adrenal gland.
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| Free Research Field |
泌尿器科、副腎腫瘍、尿路上皮癌、尿路結石
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| Academic Significance and Societal Importance of the Research Achievements |
副腎皮質移植片の再生過程におけるヘッジホッグ経路のタンパク、遺伝子を検討した研究は皆無である。本研究では移植片再生過程でShhではなくDhhの発現上昇を認めるという、これまでの通説を覆す結果を得た。DHHの副腎皮質自家移植片における組織再構築と内分泌機能獲得への関与が示唆された。
この研究成果は、副腎自家移植片の機能増強、ならびに早期生着方法を導き出し、自家移植のみならず、幹細胞移植、異種移植への応用も可能としていく。すなわち、本研究による成果は対象疾患を家族性褐色細胞腫に限定せず、ACTH非依存性副腎皮質大結節性過形成やAddison病の加療にも応用できることが期待される。
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