上睑下垂
炎症体
级联
微小变化病
疾病
细胞生物学
化学
医学
癌症研究
神经科学
免疫学
生物
炎症
内科学
肾小球肾炎
肾
局灶节段性肾小球硬化
色谱法
作者
Yuki Kajio,Taihei Suzuki,Kazuki Kobayashi,Nobuhiro Kanazawa,Masayuki Iyoda,Hirokazu Honda,Kazuho Honda
出处
期刊:Ndt Plus
[Oxford University Press]
日期:2024-07-12
卷期号:17 (8)
摘要
ABSTRACT Background In contrast to childhood minimal change disease (MCD), adult-onset MCD frequently recurs and requires prolonged immunosuppressive therapy. Accordingly, an investigation of the pathogenesis of adult MCD is required. MCD is usually accompanied by severe dyslipidaemia. Oxidized low-density lipoprotein (ox-LDL) is known to function in a damage-associated molecular pattern (DAMP) through CD36, triggering the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome and programmed cell death called pyroptosis. However, the relationship between MCD pathogenesis and NLRP3 inflammasome/pyroptosis activation via CD36 is not fully understood. Methods We conducted comprehensive histological and clinical evaluations by analysing renal biopsy (RBx) specimens and urine samples obtained from 26 patients with MCD. These samples were compared with control kidneys from 15 transplant donors and urine samples from 15 healthy volunteers. Results The number of podocytes was lower in the MCD group than in the control group. Urinary ox-LDL levels were higher in the MCD group than in the control group. Immunofluorescence staining revealed that NLRP3 and CD36 were upregulated in MCD podocytes. Urinary interleukin (IL)-18 levels increased in patients with MCD. Steroid therapy performed before RBx appeared to maintain the podocyte number and reduce urinary ox-LDL and IL-18 levels. Conclusion In MCD, the NLRP3 inflammasome and pyroptosis cascade seem to be activated via upregulation of CD36 in podocytes, associated with increased urinary ox-LDL. Elevated urinary IL-18 levels suggest that pyroptosis may occur in MCD. Further research is required to confirm the significance of the podocyte NLRP3 inflammasome/pyroptosis in MCD.
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