Do mast cell-related factors in interstitial cystitis contribute to bladder hypersensitivity?

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09354
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Dokkyo Medical University
• Principal Investigator: Aizawa Naoki 獨協医科大学, 医学部, 准教授 (80595257)
• Co-Investigator(Kenkyū-buntansha): 藤田 朋恵 獨協医科大学, 医学部, 教授 (20296510) ; 山西 友典 獨協医科大学, 医学部, 教授 (90220425)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膀胱 / 炎症 / 間質性膀胱炎 / 肥満細胞 / 知覚

Outline of Final Research Achievements

We found that gene expression of several mast cell-related receptor subtypes were upregulated in human bladder biopsy specimens from patients with interstitial cystitis/bladder pain syndrome (IC/BPS) compared with normal speciments.
Study of single unit afferent activities of rat bladder mechanosensitive afferent nerves provides evidence that histamine and H2 receptor has a physiological role of bladder sensory function. In addition, study by using newly established bladder “inside-out” preparation revealed that the bladder detrusor smooth muscle potentially has water (urine) permeability, whereas bladder mucosa has robust barrier mechanisms for preventing absorb water (urine) in at least normal rat, and that cyclophosphamide-induced cystitis bladder disrupted the bladder mucosa and drug penetration.

Free Research Field

排尿薬理学

Academic Significance and Societal Importance of the Research Achievements

IC/BPSのうち、特にICは指定難病に分類され、その病態および治療法は確立されていない。この背景に肥満細胞関連因子の関与があるか、炎症がどれだけ膀胱知覚に影響を与えるのか、はっきりとした結論は出ていなかった。
今回、患者の膀胱サンプルを用いた肥満細胞関連の脂質メディエーターの受容体発現解析と、動物実験による機能解析の結果、肥満細胞関連脂質メディエーターおよび炎症が膀胱知覚を含むIC/BPSの病態に寄与する可能性を裏付ける結果となり、今後の病態解明および治療法確立につながる研究になり得ると考える。