Abstract：
Aims: NCF1, a subunit of the NADPH oxidase 2 (NOX2), first described the expression in neutrophils and macrophages and participated in the pathogenesis from various systems. However, there are controversial findings on the role of NCF1 in different kinds of kidney diseases. In this study, we aim to pinpoint the specific role of NCF1 in the progression of renal fibrosis induced by obstruction. Results: In this study, NCF1 expression was upregulated in kidney biopsies of chronic kidney disease patients. The expression level of all subunits of the NOX2 complex was also significantly increased in the unilateral ureteral obstruction (UUO) kidney. Then, we used wild-type mice and Ncf1 mutant mice (Ncf1m1j mice) to perform UUO-induced renal fibrosis. Results demonstrated that Ncf1m1j mice exhibited mild renal fibrosis but increased macrophages count and CD11b+Ly6Chi macrophage proportion. Next, we compared the renal fibrosis degree between Ncf1m1j mice and Ncf1 macrophage-rescued mice (Ncf1m1j.Ncf1Tg-CD68 mice). We found that rescuing NCF1 expression in macrophages further alleviated renal fibrosis and decreased macrophage infiltration in the UUO kidney. In addition, flow cytometry data showed fewer CD11b+Ly6Chi macrophages in the kidney of the Ncf1m1j.Ncf1Tg-CD68 group than the Ncf1m1j group. Innovation: We first used the Ncf1m1j mice and Ncf1m1j.Ncf1Tg-CD68 mice to detect the role of NCF1 in the pathological process of renal fibrosis induced by obstruction. Also, we found that NCF1 expressed in different cell types exerts opposing effects on obstructive nephropathy. Conclusion: Taken together, our findings support that systemic mutation of Ncf1 ameliorates renal fibrosis induced by obstruction, and rescuing NCF1 in macrophages further alleviates renal fibrosis.
摘要：
目的：NCF1是NADPH氧化酶2（NOX2）的一个亚单位，首次在中性粒细胞和巨噬细胞中表达，参与了多种系统的发病机制。然而,关于NCF1在不同类型的肾脏疾病中的作用存在争议。在这里，我们的目的是明确NCF1在梗阻性肾纤维化进展中的具体作用.
结果：在这项研究中，CKD患者肾活检中NCF1表达上调。在单侧输尿管梗阻（UUO）肾脏中，NOX2复合物的所有亚基的表达水平也显着增加。然后，我们使用野生型小鼠和Ncf1突变小鼠（Ncf1m1j小鼠）进行UUO诱导的肾纤维化。结果表明，Ncf1m1j小鼠表现出轻度肾纤维化，但巨噬细胞计数和CD11b+Ly6Chi巨噬细胞比例增加。接下来,我们比较了Ncf1m1j小鼠和Ncf1巨噬细胞拯救小鼠(Ncf1m1jNcf1Tg-CD68小鼠)的肾纤维化程度。我们发现，挽救巨噬细胞中的NCF1表达进一步减轻了UUO肾脏中的肾脏纤维化并减少了巨噬细胞浸润。流式细胞术数据显示，Ncf1m1jNcf1CD68-Tg组肾脏中的CD11bLy6Chi巨噬细胞少于Ncf1m1j组。
方法：我们首先用Ncf1m1j小鼠和Ncf1m1jNcf1CD68-Tg小鼠检测NCF1在梗阻性肾纤维化病理过程中的作用。我们发现在不同细胞类型中表达的NCF1对阻塞性肾病具有相反的作用。
结论：综合来看，我们的研究结果支持Ncf1的系统性突变改善梗阻引起的肾纤维化，在巨噬细胞中挽救NCF1可进一步减轻肾脏纤维化。
结果：在这项研究中，CKD患者肾活检中NCF1表达上调。在单侧输尿管梗阻（UUO）肾脏中，NOX2复合物的所有亚基的表达水平也显着增加。然后，我们使用野生型小鼠和Ncf1突变小鼠（Ncf1m1j小鼠）进行UUO诱导的肾纤维化。结果表明，Ncf1m1j小鼠表现出轻度肾纤维化，但巨噬细胞计数和CD11b+Ly6Chi巨噬细胞比例增加。接下来,我们比较了Ncf1m1j小鼠和Ncf1巨噬细胞拯救小鼠(Ncf1m1jNcf1Tg-CD68小鼠)的肾纤维化程度。我们发现，挽救巨噬细胞中的NCF1表达进一步减轻了UUO肾脏中的肾脏纤维化并减少了巨噬细胞浸润。流式细胞术数据显示，Ncf1m1jNcf1CD68-Tg组肾脏中的CD11bLy6Chi巨噬细胞少于Ncf1m1j组。
方法：我们首先用Ncf1m1j小鼠和Ncf1m1jNcf1CD68-Tg小鼠检测NCF1在梗阻性肾纤维化病理过程中的作用。我们发现在不同细胞类型中表达的NCF1对阻塞性肾病具有相反的作用。
结论：综合来看，我们的研究结果支持Ncf1的系统性突变改善梗阻引起的肾纤维化，在巨噬细胞中挽救NCF1可进一步减轻肾脏纤维化。
