Amin Hilman Zulkifli, Sasaki Naoto, Hirata Ken-Ichi, Rikitake Yoshiyuki
Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University Kobe Japan.
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine Kobe Japan.
Circ Rep. 2020 Apr 9;2(6):339-342. doi: 10.1253/circrep.CR-20-0023.
Chronic inflammation caused by pathogenic immune response is crucial in the pathogenesis of kidney disease. In particular, T-cell-mediated adaptive immune responses evoke pathogenic immunoinflammatory responses and contribute to kidney injury (KI). Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), a potent negative regulator of T-cell immune responses, protects against immunoinflammatory diseases of the arteries such as atherosclerosis and abdominal aortic aneurysm. However, the role of this molecule in kidney disease remains undetermined. To examine the effects of CTLA-4 overexpression on angiotensin II (AngII)-induced KI, we induced KI in CTLA-4 transgenic/apolipoprotein E-deficient (CTLA-4-Tg/ ) mice or mice fed a high-cholesterol diet by continuously infusing AngII. Overexpression of CTLA-4 ameliorated the development of AngII-induced KI and fibrosis. Moreover, CTLA-4-Tg/ mice had decreased expression of pro-inflammatory molecules in the kidney. CTLA-4 overexpression has a protective effect on AngII-induced KI, and increasing CTLA-4 may be a novel therapeutic strategy to prevent the progression of kidney disease.
由致病性免疫反应引起的慢性炎症在肾脏疾病的发病机制中至关重要。特别是，T细胞介导的适应性免疫反应引发致病性免疫炎症反应并导致肾损伤（KI）。细胞毒性T淋巴细胞相关抗原4（CTLA-4）是T细胞免疫反应的一种强效负调节因子，可预防动脉免疫炎症性疾病，如动脉粥样硬化和腹主动脉瘤。然而，该分子在肾脏疾病中的作用仍未确定。为了研究CTLA-4过表达对血管紧张素II（AngII）诱导的肾损伤的影响，我们通过持续输注AngII，在CTLA-4转基因/载脂蛋白E缺陷（CTLA-4-Tg/ ）小鼠或喂食高胆固醇饮食的 小鼠中诱导肾损伤。CTLA-4的过表达改善了AngII诱导的肾损伤和纤维化的发展。此外，CTLA-4-Tg/ 小鼠肾脏中促炎分子的表达降低。CTLA-4过表达对AngII诱导的肾损伤具有保护作用，增加CTLA-4可能是预防肾脏疾病进展的一种新的治疗策略。
