Amentoflavone Induces Ferroptosis to Alleviate Proliferation, Migration, Invasion and Inflammation in Rheumatoid Arthritis Fibroblast-like Synoviocytes by Inhibiting PIN1.

IF 1.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Biochemistry and Biophysics Pub Date : 2024-10-01 DOI:10.1007/s12013-024-01563-8

Yan Ma, Hongjun Lin, Yunman Li, Zhuoling An

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引用次数: 0

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is prevalent worldwide and seriously threatens human health. RA-fibroblast-like synoviocytes (FLS) play important roles in almost all aspects of RA progression. This study aimed to study the effect of Amentoflavone (AMF), a polyphenol compound derived from extracts of Selaginella tamariscina, on the abnormal biological behaviors of RA-FLS. The immortalized human RA-FLS cell line (MH7A) was treated with AMF or transfected with small interfering RNAs (siRNAs) targeting peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Then, cell viability was detected by CCK-8 assay. EDU staining, wound healing and transwell assays were employed to measure the capacities of MH7A cell proliferation, migration and invasion. The levels of inflammatory factors were assessed using ELISA kits. Additionally, ferroptosis was analyzed by detecting Fe²⁺ content, lipid reactive oxygen species (ROS) level and expression of ferroptosis-related proteins. Pull-down assay was employed to verify the targeted binding of AMF to PIN1. Further, PIN1 overexpression or ferroptosis inhibitor Ferrostatin-1 (Fer-1) addition was conducted to elucidate the regulatory mechanism of AMF on PIN1 and ferroptosis. Results revealed that AMF intervention or PIN1 knockdown inhibited the proliferation, migration, invasion and inflammation in MH7A cells. AMF facilitated lipid peroxidation and ferroptosis in MH7A cells. Moreover, AMF targeted inhibition of PIN1 expression, and PIN1 overexpression restored the promoting effect of AMF on lipid peroxidation and ferroptosis in MH7A cells. Besides, Fer-1 reversed the impacts of AMF on the abnormal biological behaviors of MH7A cells. In summary, AMF induced ferroptosis to inhibit the proliferation, migration, invasion and inflammation in RA-FLS by inhibiting PIN1, providing a promising candidate for RA treatment.

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门冬酰胺黄酮通过抑制 PIN1 诱导铁变态反应，从而缓解类风湿性关节炎成纤维细胞样滑膜细胞的增殖、迁移、侵袭和炎症。

类风湿性关节炎（RA）是一种全身性自身免疫性疾病，在全球流行，严重威胁人类健康。类风湿关节炎纤维样滑膜细胞（FLS）在类风湿关节炎的几乎所有进展过程中都发挥着重要作用。本研究的目的是研究从柽柳属植物提取物中提取的多酚化合物--门黄酮（AMF）对 RA-FLS 异常生物学行为的影响。用AMF处理永生化的人RA-FLS细胞系（MH7A），或转染靶向肽基脯氨酰顺反异构酶NIMA-interacting 1（PIN1）的小干扰RNA（siRNA）。然后用 CCK-8 法检测细胞活力。采用 EDU 染色法、伤口愈合法和透孔法检测 MH7A 细胞的增殖、迁移和侵袭能力。使用 ELISA 试剂盒评估了炎症因子的水平。此外，还通过检测 Fe2+ 含量、脂质活性氧（ROS）水平和铁变态反应相关蛋白的表达来分析铁变态反应。采用牵引试验验证了 AMF 与 PIN1 的靶向结合。此外，还通过过表达 PIN1 或添加铁突变抑制剂 Ferrostatin-1 (Fer-1) 来阐明 AMF 对 PIN1 和铁突变的调控机制。结果发现，AMF干预或PIN1敲除可抑制MH7A细胞的增殖、迁移、侵袭和炎症反应。AMF促进了MH7A细胞的脂质过氧化和铁蛋白沉积。此外，AMF靶向抑制了PIN1的表达，而PIN1的过表达则恢复了AMF对MH7A细胞脂质过氧化和铁突变的促进作用。此外，Fer-1能逆转AMF对MH7A细胞异常生物学行为的影响。综上所述，AMF通过抑制PIN1诱导铁变态反应，从而抑制了RA-FLS细胞的增殖、迁移、侵袭和炎症，为RA的治疗提供了一种很有前景的候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

7.5 months

期刊介绍： Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.