Renal vascular dysfunction and acute glomerulonephritis by haemolytic exotoxin fromStreptococcus pyogenes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06568
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Okayama University of Science
• Principal Investigator: Takeya Kosuke 岡山理科大学, 獣医学部, 講師 (20586862)
• Co-Investigator(Kenkyū-buntansha): 三河 翔馬 岡山理科大学, 獣医学部, 助教 (20845664)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腎微小循環 / 溶連菌毒素 / Streptolysin O

Outline of Final Research Achievements

In this study, we investigated the effects of the streptococcal toxin Streptolysin O (SLO) on the exacerbation of PSAGN. While SLO is known to form pores in cell membranes, causing cell destruction and inflammatory responses, no PSAGN-like lesions were observed in the kidneys of rats administered SLO alone. When examining the effects of SLO on isolated renal afferent and efferent arterioles, it was found that SLO suppressed Angiotensin II-induced contraction and enhanced Acetylcholine-induced relaxation in the afferent arterioles, without affecting the efferent arterioles. In isolated kidney perfusion experiments, SLO did not inhibit Angiotensin II-induced vasoconstriction but induced biphasic relaxation in response to Acetylcholine. These results reveal that while SLO affects renal microcirculation, it did not demonstrate a direct involvement in the exacerbation of PSAGN.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

溶連菌感染後急性糸球体腎炎（PSAGN）は、小児から成人まで幅広い年齢層に影響を与える腎疾患である。多くの症例は自然治癒するが、一部の患者では慢性腎不全へと進行する。PSAGNの増悪メカニズムは完全には解明されておらず、治療戦略確立への解明が期待されている。これまでPSAGN発症機序は溶連菌の外毒素の一部(スーパー抗原)がIII型アレルギーを誘発し、糸球体の細胞に炎症を引き起こすメカニズムが明らかとなっている。本研究では、溶連菌が産生する細胞外毒素の一つであるStreptolysin O（SLO）が腎血管機能を変調することが明らかとなり、PSAGNの増悪プロセスに関わる可能性が示された。