Upregulation of allograft inflammatory factor‑1 expression and secretion by macrophages stimulated with aldosterone promotes renal fibroblasts to a profibrotic phenotype.
Upregulation of allograft inflammatory factor‑1 expression and secretion by macrophages stimulated with aldosterone promotes renal fibroblasts to a profibrotic phenotype.
复制标题
醛固酮刺激的巨噬细胞上调同种异体移植物炎症因子 1 的表达和分泌，促进肾成纤维细胞形成促纤维化表型
DOI：
10.3892/ijmm.2018.3667
复制
发表时间：
2018-08
影响因子：
5.4
通讯作者：
Hao L
中科院分区：
文献类型：
--
作者：
Li Y;Wang X;Zhang L;Yuan X;Hao J;Ni J;Hao L
巨噬细胞已被确定为肾间质纤维化（RIF）发病机制的关键细胞类型。然而，巨噬细胞驱动纤维化的机制尚不清楚。目前的研究重点是同种异体移植炎症因子-1 （AIF-1）的作用和可能的潜在机制，AIF-1是一种由巨噬细胞表达和分泌的炎症反应性支架蛋白，在促进成纤维细胞向纤维化表型的过程中。体内实验表明，单侧输尿管梗阻小鼠肾组织中AIF-1、CD68和α-平滑肌肌动蛋白（α-SMA）表达上调，醛固酮受体拮抗剂螺内酯抑制其表达。双免疫荧光染色显示AIF-1的表达与cd68阳性的巨噬细胞在肾间质共定位，表明在RIF动物模型中，巨噬细胞中AIF-1的表达增加。此外，为了确定AIF-1在促进纤维化中的作用，我们在体外检测了其在RAW264.7巨噬细胞中的表达和分泌。与巨噬细胞共培养后，检测成纤维细胞中α-SMA、磷酸化p38 （p-p38）和纤维连接蛋白（FN）的表达水平。在RAW264.7细胞中，AIF-1的表达和分泌增加是对醛固酮的反应。醛固酮刺激成纤维细胞与巨噬细胞共培养72 h后，可诱导成纤维细胞α-SMA表达，FN和p-p38表达水平显著升高。此外，用AIF-1小干扰RNA稳定转染RAW264.7细胞可降低AIF-1的表达，导致与巨噬细胞共培养的成纤维细胞中α-SMA、p-p38和FN的表达水平较正常巨噬细胞显著降低。这些发现表明，巨噬细胞中AIF-1的表达对于肾成纤维细胞活化成纤维化表型至关重要。巨噬细胞中AIF-1表达上调，可能是巨噬细胞通过p38信号通路促进RIF的新机制。
Macrophages have been identified as a key cell type in the pathogenesis of renal interstitial fibrosis (RIF). However, the mechanism through which macrophages drive fibrosis remains unclear. The current study focuses on the effects and possible underlying mechanism of allograft inflammatory factor-1 (AIF-1), an inflammation-responsive scaffold protein expressed and secreted by macrophages, in promoting fibroblasts to a profibrotic phenotype. In vivo experiments indicated that AIF-1, CD68 and α-smooth muscle actin (α-SMA) were upregulated in kidney tissues of mice subjected to unilateral ureteric obstruction, while their expressions were inhibited by an aldosterone receptor antagonist, spironolactone. Double immunofluorescence staining revealed that AIF-1 expression co-localized with CD68-positive macrophages in the renal interstitium, indicating that AIF-1 expression in macrophages was increased in the RIF animal model. Furthermore, to identify the role of AIF-1 in promoting fibrosis, its expression and secretion by the RAW264.7 macrophage cell line were detected in vitro. The expression levels of α-SMA, phosphorylated p38 (p-p38) and fibronectin (FN) in fibroblasts were examined subsequent to co-culture with macrophages. The increase in AIF-1 expression and secretion was confirmed in RAW264.7 cells in response to aldosterone. After 72 h of co-culture between fibroblasts and macrophages stimulated with aldosterone, the α-SMA expression was induced in fibroblasts, with significantly increased expression levels of FN and p-p38 observed. In addition, AIF-1 expression was reduced by stable transfection of RAW264.7 cells with AIF-1 small interfering RNA, resulting in significantly reduced expression levels of α-SMA, p-p38 and FN in fibroblasts co-cultured with macrophages as compared with normal macrophages. These findings indicate that the expression of AIF-1 in macrophages is critical for the activation of renal fibroblasts to a profibrotic phenotype. AIF-1 expression was upregulated in macrophages, and may be a novel mechanism linking macrophages to the promotion of RIF via the p38 signaling pathway.
登录
查看更多内容
影响因子：
3.2
作者：
Farris AB;Colvin RB
通讯作者：
Colvin RB
DOI：
10.1006/bbrc.1996.1112
发表时间：
1996-07-25
影响因子：
3.1
作者：
Imai, Y;Ibata, I;Kohsaka, S
通讯作者：
Kohsaka, S
影响因子：
2.5
作者：
Bengough, A. Glyn;Hans, Joachim;Valentine, Tracy A.
通讯作者：
Valentine, Tracy A.
DOI：
10.1016/j.bbrc.2014.04.106
发表时间：
2014-06-06
影响因子：
3.1
作者：
Kadoya, Masatoshi;Yamamoto, Aihiro;Kawahito, Yutaka
通讯作者：
Kawahito, Yutaka
DOI：
10.1007/s00467-017-3883-1
发表时间：
2019-04
期刊：
Pediatric nephrology (Berlin, Germany)
影响因子：
--
作者：
Han HI;Skvarca LB;Espiritu EB;Davidson AJ;Hukriede NA
通讯作者：
Hukriede NA