Jinying Zhao1, Bo Chen2, Xiaodong Peng3, Chunyu Wang1, Kejing Wang1, Fengxia Han1, Jin Xu1. 1. Department of Rheumatism and Immunology, The 940th Hospital of Joint Logistics Support Force of People's Liberation Army, Lanzhou, China. 2. Department of Emergency, The 940th Hospital of Joint logistics Support Force of People's Liberation Army, Lanzhou, China. 3. Department of Pharmacology, Ningxia Medical University, Ningxia Hui Autonomous Region, Yinchuan, China.
Abstract
Background: Rheumatoid arthritis (RA) is a systematic autoimmune disease which may lead to joint dysfunction and disability. Aberrant migration and invasion of fibroblast-like synoviocytes (FLSs) is one of the most predominant etiopathogenesis of RA. Quercetin is a bioflavonoid which is implicated in the development of RA, yet its role in regulating the migration and invasion of FLSs is still elusive. The aim of this study is to investigate the impact of quercetin treatment on migration and invasion of FLSs and the underlying mechanism. Methods: Capacity of migration and invasion of FLSs were assessed using transwell assay. Immunofluorescence assay was used to determine the expression of F-actin. The RNA levels of miR-146a and GATA transcription factor 6 (GATA6) were measured using quantitative real-time PCR. Western blot was used to examine the protein level of GATA6. The correlation between miR-146a and GATA6 was validated using luciferase reporter assay. Results: Transwell assay revealed that the migration and invasion of FLSs were significantly inhibited after quercetin treatment, which was also proved by decreased expression of F-actin. The RNA level of miR-146a was decreased in RA tissues and was negatively related to the expression of GATA transcription factor 6 (GATA6). Quercetin treatment elevated the RNA level of miR-146a, but suppressed the expression of GATA6 in FLSs. Further luciferase reporter assay validated that GATA6 is a downstream target of miR-146a. Besides, miR-146a inhibited the migration and invasion of FLSs, and further GATA6 over-expression abrogated the miR-146a-induced inhibition. In addition, specific anti-miR-146a inhibitor abolished quercetin-mediated suppression of migration and invasion of FLSs. Conclusion: Our study suggested that quercetin suppresses the migration and invasion of FLSs via regulating the miR-146a/GATA6 axis.
Background: Rheumatoid arthritis (RA) is a systematic autoimmune disease which may lead to joint dysfunction and disability. Aberrant migration and invasion of fibroblast-like synoviocytes (FLSs) is one of the most predominant etiopathogenesis of RA. Quercetin is a bioflavonoid which is implicated in the development of RA, yet its role in regulating the migration and invasion of FLSs is still elusive. The aim of this study is to investigate the impact of quercetin treatment on migration and invasion of FLSs and the underlying mechanism. Methods: Capacity of migration and invasion of FLSs were assessed using transwell assay. Immunofluorescence assay was used to determine the expression of F-actin. The RNA levels of miR-146a and GATA transcription factor 6 (GATA6) were measured using quantitative real-time PCR. Western blot was used to examine the protein level of GATA6. The correlation between miR-146a and GATA6 was validated using luciferase reporter assay. Results: Transwell assay revealed that the migration and invasion of FLSs were significantly inhibited after quercetin treatment, which was also proved by decreased expression of F-actin. The RNA level of miR-146a was decreased in RA tissues and was negatively related to the expression of GATA transcription factor 6 (GATA6). Quercetin treatment elevated the RNA level of miR-146a, but suppressed the expression of GATA6 in FLSs. Further luciferase reporter assay validated that GATA6 is a downstream target of miR-146a. Besides, miR-146a inhibited the migration and invasion of FLSs, and further GATA6 over-expression abrogated the miR-146a-induced inhibition. In addition, specific anti-miR-146a inhibitor abolished quercetin-mediated suppression of migration and invasion of FLSs. Conclusion: Our study suggested that quercetin suppresses the migration and invasion of FLSs via regulating the miR-146a/GATA6 axis.
Authors: Mengshi Tang; Yan Zeng; Weijun Peng; Xi Xie; Yongyu Yang; Biting Ji; Fen Li Journal: Drug Des Devel Ther Date: 2022-06-29 Impact factor: 4.319