Elucidation of the mechanism of compensatory hyperfunction of salivary glands and induction of enhancement of secretion using in vivo functional analysis.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09882
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: Nezu Akihiro 北海道医療大学, 歯学部, 准教授 (00305913)
• Co-Investigator(Kenkyū-buntansha): 森田 貴雄 日本歯科大学, 新潟生命歯学部, 教授 (20326549) ; 細矢 明宏 北海道医療大学, 歯学部, 教授 (70350824)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 唾液分泌 / 代償性肥大 / 機能亢進 / Ca2+応答 / in vivo機能解析

Outline of Final Research Achievements

When one side of the salivary gland is dysfunctional, the remaining gland compensates for the low salivary secretion by compensatory hypertrophy. By simultaneously monitoring the Ca2+ response and salivary secretion of the submandibular gland in living animals, we have shown that signals causing compensatory hypertrophy induce the remaining submandibular gland to become a hyperfunctioning gland. Comprehensive gene analysis of submandibular gland tissue identified 6 marker genes associated with hyperfunctioning glands. Furthermore, the quantitative analysis of these marker genes changes revealed the involvement of parasympathetic nervous system transmitters as signals for induction of this hyperfunction due to the unilateral submandibular glands dysfunction. Measurement of the number of cell growth factor-positive cells suggested that differentiation from ductal cells to acinar cells and proliferation of acinar cells were occurring in the hyperfunctioning glands.

Free Research Field

歯科薬理学

Academic Significance and Societal Importance of the Research Achievements

本課題では、唾液腺のCa2+応答と唾液分泌を同時に測定可能なin vivo機能解析法を用いて、唾液腺の代償性肥大は単なる腺肥大ではなく分泌刺激に対する感受性が亢進した機能亢進腺へ誘導することを明らかにした。また機能亢進腺の網羅的遺伝子変動解析により、機能亢進腺で変化するマーカー遺伝子を同定し、それらを用いて副交感神経系伝達物質が誘導シグナルとして働くことを示した。さらにマーカー遺伝子変動や増殖因子の陽性細胞数計測により、このシグナルは導管から腺房へ分化と細胞増殖に関与する可能性が示された。得られた知見は、生体が持つ自己回復能の誘導による全く新しいドライマウス治療法への応用が期待できる。