INSERM Unit 1073, University of Rouen, CEDEX, 76183 Rouen, France.
Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, CEDEX, 76183 Rouen, France.
Nutrients. 2022 Aug 9;14(16):3253. doi: 10.3390/nu14163253.
Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD) patients without specific treatment. Aryl hydrocarbon receptor (AhR) activation is associated with better outcomes in intestinal inflammation. Development of novel therapies targeting fibrogenic pathways is required and we aimed to screen dietary AhR ligands for their anti-fibrotic properties in TGF-β1-stimulated human colonic fibroblast cells.
The study was conducted using TGF-β1-stimulated CCD-18Co, a human colonic fibroblast cell line in response to increased concentrations of dietary ligands of AhR such as FICZ, ITE, L-kynurenine and curcumin. Fibrosis markers such as α-SMA, COL1A1, COL3A1 and CTGF were assessed. AhR and ANRT RNA were evaluated.
TGF-β1 at 10 ng/mL significantly induced mRNA levels for ECM-associated proteins such as CTGF, COL1A1 and COL3A1 in CCD-18Co cells. FICZ from 10 to 1000 nM, L-kynurenine from 0.1 to 10 μM, ITE from 1 to 100 μM or curcumin from 5 to 20 μM had no significant effect on fibrosis markers in TGF-β1-induced CCD-18Co.
Our data highlight that none of the tested dietary AhR ligands had an effect on fibrosis markers in TGF-β1-stimulated human colonic fibroblast cells in our experimental conditions. Further studies are now required to identify novel potential targets in intestinal fibrosis.
肠纤维化是炎症性肠病（IBD）患者的常见并发症，目前尚无特异性治疗方法。芳香烃受体（AhR）的激活与肠道炎症的改善结果相关。需要开发针对纤维生成途径的新型治疗方法，我们旨在筛选膳食 AhR 配体，以研究其在 TGF-β1 刺激的人结肠成纤维细胞中抗纤维化的特性。
本研究使用 TGF-β1 刺激的 CCD-18Co 人结肠成纤维细胞系进行，该细胞系对 AhR 的膳食配体（如 FICZ、ITE、L-犬尿氨酸和姜黄素）的浓度增加作出反应。评估纤维化标志物如 α-SMA、COL1A1、COL3A1 和 CTGF。评估 AhR 和 ANRT RNA。
TGF-β1（10ng/mL）显著诱导 CCD-18Co 细胞中 ECM 相关蛋白的 mRNA 水平，如 CTGF、COL1A1 和 COL3A1。FICZ（10 至 1000 nM）、L-犬尿氨酸（0.1 至 10 μM）、ITE（1 至 100 μM）或姜黄素（5 至 20 μM）对 TGF-β1 诱导的 CCD-18Co 细胞中的纤维化标志物没有显著影响。
我们的数据表明，在我们的实验条件下，测试的膳食 AhR 配体均未对 TGF-β1 刺激的人结肠成纤维细胞中的纤维化标志物产生影响。目前需要进一步研究以确定肠道纤维化的新潜在靶点。
