心肌营养素-1(CT-1),白细胞介素(IL)-6细胞因子家族的成员,在急性肾脏疾病和肾小管间质纤维化的小鼠模型中具有肾脏保护作用,但其在肾小球疾病中的作用尚不清楚。为了解决这个问题,我们使用肾毒性肾炎小鼠模型来检验CT-1在免疫介导的肾小球疾病中也具有保护作用的假设.使用免疫组织化学和分析分离的肾小球的单细胞RNA测序数据,我们证明了CT-1在雄性小鼠的肾小球中表达,主要在壁上皮细胞中,在肾毒性肾炎小鼠中下调。此外,对患者数据的分析显示,人类肾小球疾病也与肾小球CT-1转录水平降低相关.在患有肾毒性肾炎和建立蛋白尿的雄性小鼠中,给予CT-1导致蛋白尿减少,防止足细胞损失,和持续的血浆肌酐,与给予生理盐水的小鼠相比。CT-1治疗也减少了肾皮质的纤维化,肾小球周围巨噬细胞积累和肾脏水平的促炎介质补体成分5a。总之,CT-1干预治疗通过保留肾功能和抑制肾脏炎症和纤维化延缓小鼠肾小球疾病的进展.
Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 cytokine family, has renoprotective effects in mouse models of acute kidney disease and tubulointerstitial fibrosis, but its role in glomerular disease is unknown. To address this, we used the mouse model of nephrotoxic nephritis to test the hypothesis that CT-1 also has a protective role in immune-mediated glomerular disease. Using immunohistochemistry and analysis of single-cell RNA-sequencing data of isolated glomeruli, we demonstrate that CT-1 is expressed in the glomerulus in male mice, predominantly in parietal epithelial cells and is downregulated in mice with nephrotoxic nephritis. Furthermore, analysis of data from patients revealed that human glomerular disease is also associated with reduced glomerular CT-1 transcript levels. In male mice with nephrotoxic nephritis and established proteinuria, administration of CT-1 resulted in reduced albuminuria, prevented podocyte loss, and sustained plasma creatinine, compared with mice administered saline. CT-1 treatment also reduced fibrosis in the kidney cortex, peri-glomerular macrophage accumulation and the kidney levels of the pro-inflammatory mediator complement component 5a. In conclusion, CT-1 intervention therapy delays the progression of glomerular disease in mice by preserving kidney function and inhibiting renal inflammation and fibrosis.