The Department of Biomedical Engineering, University of Houston, Houston, TX 77204-5060, USA.
The Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-0000, USA.
Int J Mol Sci. 2021 Feb 19;22(4):2059. doi: 10.3390/ijms22042059.
The 129sv mouse strain is particularly sensitive to experimental immune-mediated nephritis. Previous studies have indicated that transforming growth factor-β (TGF-β) plays a critical role in both immune modulation and tissue fibrogenesis in various diseases and that its biological activities are exerted via the SMAD family. In this study, we aimed to determine whether TGF-β/SMAD signaling is essential for the development of immune-mediated nephritis in 129sv mice. Relative to C57BL/6J control mice with anti-glomeruli basement membrane (GBM) nephritis, 129sv mice with anti-GBM nephritis exhibited increased renal collagen deposition. Additionally, higher mRNA levels of pro-collagen and collagen IV, higher serum levels of active and total TGF-β1, and increased TGF-β1, TGF-βIIR, and phosphorylated SMAD expression were detected in these mice. Deletion of in 129sv mice ameliorated anti-GBM induced nephritis, including crescentic glomerulonephritis. Collectively, these findings indicate that the heightened experimental nephritis and fibrotic disease in the 129sv strain of mice are regulated by SMAD3, which could be a potential therapeutic target for immune-mediated nephritis.
129sv 小鼠品系对实验性免疫介导性肾炎特别敏感。先前的研究表明，转化生长因子-β（TGF-β）在各种疾病的免疫调节和组织纤维化中起着关键作用，其生物学活性通过 SMAD 家族发挥作用。在本研究中，我们旨在确定 TGF-β/SMAD 信号通路是否对 129sv 小鼠免疫介导性肾炎的发展至关重要。与具有抗肾小球基底膜（GBM）肾炎的 C57BL/6J 对照小鼠相比，患有抗 GBM 肾炎的 129sv 小鼠表现出更高的肾脏胶原沉积。此外，这些小鼠的前胶原和胶原 IV 的 mRNA 水平更高，血清中活性和总 TGF-β1 水平更高，TGF-β1、TGF-βIIR 和磷酸化 SMAD 的表达增加。在 129sv 小鼠中缺失 可改善抗 GBM 诱导的肾炎，包括新月体肾小球肾炎。总之，这些发现表明，129sv 小鼠品系中实验性肾炎和纤维化疾病的加重受 SMAD3 调节，SMAD3 可能是免疫介导性肾炎的潜在治疗靶点。
