Role of TRPV4 in interstitial cystitis/bladder pain syndrome

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09228
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Yoshizumi Masaru 東北医科薬科大学, 薬学部, 講師 (70553379)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 間質性膀胱炎 / 膀胱痛症候群 / LPS / TRPV4 / 炎症性サイトカイン / マクロファージ

Outline of Final Research Achievements

We investigated the potential benefit of intravesical TRPV4 agonist for painful bladder hypersensitivity produced by a rat model of LPS-induced cystitis and whether its effects modulate the LPS signal for cytokine release and macrophage phenotype change. The increased bladder pain-related behaviors and voiding frequency caused by LPS were suppressed by concurrent injection into the rat bladder of a selective TRPV4 agonist, GSK1016790A. Moreover, the production and secretion of proinflammatory cytokines (e.g., CXCL1, CXCL10), are suppressed by the presence of GSK1016790A. Furthermore, TRPV4 activation switched the LPS-stimulated pro-inflammatory M1-type macrophage to the anti-inflammatory M2-type macrophage. These results suggest that that activation of TRPV4 in bladder regulates the proinflammatory response by LPS, and TRPV4 functions may be a promising future therapeutic target for refractory chronic cystitis.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

間質性膀胱炎・膀胱痛症候群は原因が未だ不明であり、治療には膀胱水圧拡張術や50%DMSO膀胱内注入療法があるが、治療効果は一時的でしばしば再燃するため根治治療が急務となる。本研究は、膀胱に局在するTRPV4がLPS誘発性の炎症反応に対して抗炎症へと働くことが確認できた。本研究結果により、TRPV4アゴニストが間質性膀胱炎・膀胱痛症候群に対する新規治療の候補として今後期待できる。