The role of endoplasmic reticulum stress in endocrinopathy associated with IgG4 related disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17518
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Takeshima Ken 和歌山県立医科大学, 医学部, 講師 (40647517)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: IgG4関連疾患 / IgG4-RD

Outline of Final Research Achievements

In this research, we attempted to develop an animal model of IgG4-related disease and to clarify the role of endoplasmic reticulum stress in endocrinopathy associated with IgG4 related disease.
We firstly injected serum IgGs from patients with IgG4-related disease to neonatal mice　and evaluated pathological features of the pancreas; deposition of IgG4 antibodies at the interstitial area between pacreatic acinar cells.
We also immunized Laminin511, a potential corresponding antigen of IgG4 antibodies, with BALB/C mice and evaluated the glucose tolerance. IPGTT revelaed that the serum glucose levels are higher in Laminin 511 group than in control group after 15 minites of glucose stimulation, but not significantly. In addition, mRNA expressions associated with endoplasmic reticulum stress showed no differences between the groups.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究は、IgG4関連疾患モデルマウスの作成を試み、未だ検討が行われていない IgG4 関連疾患に伴う内分泌異常と小胞体ストレスの関連性に着目した点で意義がある。本研究で患者血清由来IgGsおよびLaminin511を用いたIgG4関連疾患モデルマウスでは、十分な炎症細胞浸潤と小胞体ストレスの亢進が認められなかった。しかし、今後小胞体ストレス亢進を伴うモデルマウスを作成できれば、小胞体ストレスを減弱するKIRAが新たな治療選択となりうるため、将来的に新たな治療法への応用につながる可能性があり、この点において意義がある。