Influence of FOSL1 Inhibition on Vascular Calcification and ROS Generation through Ferroptosis via P53-SLC7A11 Axis

被引:6
|
作者
Shao, Sisi [1 ,2 ]
Liu, Yaoxin [1 ,2 ]
Hong, Wanzi [1 ,2 ]
Mo, Yuanxi [1 ]
Shu, Fen [1 ,2 ]
Jiang, Lei [2 ,3 ]
Tan, Ning [1 ,2 ]
机构
[1] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Guangdong Cardiovasc Inst, Guangdong Prov Key Lab Coronary Heart Dis Prevent,, Guangzhou 510080, Peoples R China
[2] South China Univ Technol, Sch Med, Guangzhou 510080, Peoples R China
[3] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Guangdong Prov Geriatr Inst, Guangzhou 510080, Peoples R China
关键词
FOSL1; vascular calcification; ferroptosis; SMOOTH-MUSCLE-CELL; CHRONIC KIDNEY-DISEASE; ARTERIAL CALCIFICATION; AP-1; SENESCENCE; CULTURE; TARGET; DAMAGE; DEATH;
D O I
10.3390/biomedicines11020635
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Vascular calcification during aging is highly prevalent in patients with cardiovascular disease; however, there is still no improvement in clarifying the development of vascular calcification. FOSL1 is a transcription regulator belonging to the AP-1 family, which has a unique function in vascular senescence, but its role in vascular calcification needs to be further explored. Methods: Primary mouse vascular smooth muscle cells were isolated and used to construct a calcification model in vitro. Seven-week-old male C57BL/6 mice were used to build the vitD3-induced calcification model in vivo. qRT-PCR and western blot were used to verify the expression of FOSL1 and other genes expressed in vascular smooth muscle cells and aortas. The level of calcification was determined by Alizarin Red S (ARS) staining and the calcium content assay. The level of cellular GSH was detected by the GSH assay kit. Results: Here, we report that FOSL1 was up-regulated after high-calcium/phosphate treatment in both the in vivo and in vitro vascular calcification models. Functional studies have shown that the reduction of FOSL1 attenuates ferroptosis and calcification in vascular smooth muscle cells, as indicated by ARS staining, calcium content assay, and western blot. The inhibition of FOSL1 downregulated the expression of bone-related molecules including Msh Homeobox 2 (MSX2) and tumor necrosis factor receptor superfamily, member 11b/osteoprotegerin (OPG), suggesting that FOSL1 promoted osteogenic differentiation of vascular smooth muscle cells. Furthermore, we found that the ferroptosis-inducing drug erastin can significantly accelerate calcification in the aortic ring while Ferrostatin-1 (fer-1), a drug to protect cells from ferroptosis, can alleviate calcification. Further experiments have shown that inhibiting FOSL1 can promote the expression of ferroptosis-related genes and attenuate calcification. Functionally, cellular GSH levels were increased after the reduction of FOSL1. Conclusions: In this study, we observed a significant protective effect when we reduced the expression of FOSL1 during vascular calcification, and this effect might regulate ferroptosis to a great extent.
引用
收藏
页数:13
相关论文
共 50 条
  • [21] Wogonoside attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis through SOCS1/P53/SLC7A11 pathway
    Liu, Guofang
    Wei, Can
    Yuan, Siyu
    Zhang, Zhe
    Li, Jiahao
    Zhang, Lijun
    Wang, Guokai
    Fang, Ling
    PHYTOTHERAPY RESEARCH, 2022, 36 (11) : 4230 - 4243
  • [22] Ulinastatin ameliorates podocyte ferroptosis via regulating miR-144-3p/SLC7A11 axis in acute kidney injury
    Xiaosong Yang
    Na Guo
    In Vitro Cellular & Developmental Biology - Animal, 2023, 59 (9) : 697 - 705
  • [23] Ulinastatin ameliorates podocyte ferroptosis via regulating miR-144-3p/SLC7A11 axis in acute kidney injury
    Yang, Xiaosong
    Guo, Na
    IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, 2023, 59 (09) : 697 - 705
  • [24] STAT6 inhibits ferroptosis and alleviates acute lung injury via regulating P53/SLC7A11 pathway
    Yang, Youjing
    Ma, Yu
    Li, Qianmin
    Ling, Yi
    Zhou, Yujia
    Chu, Kaimiao
    Xue, Lian
    Tao, Shasha
    CELL DEATH & DISEASE, 2022, 13 (06)
  • [25] STAT6 inhibits ferroptosis and alleviates acute lung injury via regulating P53/SLC7A11 pathway
    Youjing Yang
    Yu Ma
    Qianmin Li
    Yi Ling
    Yujia Zhou
    Kaimiao Chu
    Lian Xue
    Shasha Tao
    Cell Death & Disease, 13
  • [26] Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway
    HE Dan
    TAN Xiaoning
    LI Linpei
    GAO Wenhui
    TIAN Xuefei
    ZENG Puhua
    Chinese Journal of Integrative Medicine, 2024, 30 (11) : 1001 - 1006
  • [27] SOX4 inhibits ferroptosis and promotes proliferation of endometrial cancer cells via the p53/SLC7A11 signaling
    Zhu, Hongli
    Xu, Song
    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH, 2024,
  • [28] SHARPIN promotes cell proliferation of cholangiocarcinoma and inhibits ferroptosis via p53/SLC7A11/GPX4 signaling
    Zeng, Chong
    Lin, Jie
    Zhang, Ketao
    Ou, Huohui
    Shen, Ke
    Liu, Qingbo
    Wei, Zibo
    Dong, Xinhuai
    Zeng, Xiaokang
    Zeng, Liming
    Wang, Weidong
    Yao, Jie
    CANCER SCIENCE, 2022, 113 (11) : 3766 - 3775
  • [29] Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway
    He, Dan
    Tan, Xiao-ning
    Li, Lin-pei
    Gao, Wen-hui
    Tian, Xue-fei
    Zeng, Pu-hua
    CHINESE JOURNAL OF INTEGRATIVE MEDICINE, 2024, 30 (11) : 1001 - 1006
  • [30] NOBILETIN AMELIORATES HEATSTROKE-INDUCED ACUTE LUNG INJURY BY INHIBITING FERROPTOSIS VIA P53/SLC7A11 PATHWAY
    Chen, Hui
    Xie, Weidang
    Peng, Zanling
    Liu, Yanan
    Li, Hongbo
    Huang, Wei
    SHOCK, 2024, 61 (01): : 105 - 111