Analysis of functional diversity and disease relevance of secretogranin III

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06418
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Nihon University
• Principal Investigator: GOMI Hiroshi 日本大学, 生物資源科学部, 教授 (90293240)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 内分泌顆粒 / セクレトグラニン3 / セクレトグラニン2 / 副腎髄質 / 神経膠細胞 / クロム親和性細胞 / 褐色細胞腫 / 伴侶動物

Outline of Final Research Achievements

We analyzed the expression of the LacZ reporter gene in secretogranin III (Sg3) gene-trap mice and found expression in neurons, glial cells, and adrenal medullary cells, in addition to known peptide hormone-secreting cells. In glioma cells, Sg3 expression was enhanced by glutamate stimulation. Co-expression with vesicular monoamine transporter 2 (VMAT2) was detected immunohistochemically in canine adrenal medullary cells, but the coexpression pattern was different from that of Sg2. There was no significant interaction between Sg3 and VMAT2 detected by co-immunoprecipitation and pull-down assay. In patient dogs with pheochromocytoma, Sg3 showed similar expression kinetics to chromogranin A, but different from Sg2. Our results contribute to a new understanding of the molecular characteristics of Sg3 and the pathogenesis of related diseases in veterinary fields.

Free Research Field

内分泌細胞学

Academic Significance and Societal Importance of the Research Achievements

Sg3はペプチドホルモン産生細胞においてホルモン顆粒の形成に関与する分子として知られている。ニワトリ，マウス，イヌおよびウシといった動物種における個体レベルでの発現解析によってペプチドホルモン産生細胞以外の多様な細胞でSg3が発現し，神経膠細胞や副腎カテコルアミン細胞での発現動態からSg3の機能的多様性が示唆された。また，Sg3の機能的類似分子として位置付けられるSg2との明確な差異が組織学レベルで明らかとなった。伴侶動物の腫瘍組織におけるグラニンタンパク質の発現動態の解析は初めての報告であり，獣医学領域の神経内分泌疾患の病態病理の理解につながる知見である。