TRIM7 promotes proliferation and migration of vascular smooth muscle cells in atherosclerosis through activating c‐Jun/AP‐1

Abstract

Atherosclerosis (AS), with associated risk of stroke or cerebrovascular disease, is one of the most common causes of death globally. It has been well established that tripartite motif‐containing protein 7 Tripartite Motif‐containing 7 (Trim7), as an E3 ubiquitin protein ligase, is involved in protein ubiquitination and thus regulating cellular proliferation. Moreover, TRIM7 is upregulated in advanced carotid AS. However, the detailed mechanism of TRIM7 on regulation of AS remains unclear. In the present study, we firstly discovered that TRIM7 expression was robustly induced in platelet‐derived growth factor type BB‐treated vascular smooth muscle cells (VSMCs) and human atherosclerotic plaques. Functional approaches established that knockdown of TRIM7 inhibited proliferation and migration of VSMCs, as well as arrested the cell cycle at G1‐S, thus suppressing AS progression. Our results also identified that c‐Jun/activator protein 1 (AP‐1) signaling pathway was activated by TRIM7. Moreover, gain‐ and loss‐of‐function studies revealed that TRIM7 could promote proliferation and migration of VSMCs via activation of c‐Jun/AP‐1 signaling pathway. Finally, by using atherogenic apolipoprotein E‐deficient (apoE–/–) C57BL/6 mice with high‐fat diet AS model, we demonstrated that interference of TRIM7 could effectively mitigate in vivo AS via inactivation of c‐Jun/AP‐1 signaling pathway. In general, activation of c‐Jun/AP‐1 signaling pathway via TRIM7 could be an important mechanism in AS progression, thus shedding light on the development of novel therapeutics to the treatment of the disease.

Enhancer of zeste homolog 2 participates in the process of atherosclerosis by modulating microRNA‐139‐5p methylation and signal transducer and activator of transcription 1 expression

“…AS, with connected risk of stroke or cerebrovascular illness, is a familiar cause of death in the world. 26 There are some miRNAs connected with AS. For example, excessive expression of miR-377 could be an effective therapeutic method for AS.…”

“…AS, with connected risk of stroke or cerebrovascular illness, is a familiar cause of death in the world 26 . There are some miRNAs connected with AS.…”

Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

“…C-Jun promotes dedifferentiation of SCs and overexpression of c-Jun alone might be sufficient to reprogram SCs of intact nerves into repair phenotype [27]. C-Jun signaling involved in promoting many cell proliferation and migration [20,28,29]. C-Jun-modified SCs showed enhanced proliferation and migration abilities [20].…”

Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1

“…In particular, TRIM7 was initially identified through its interaction with GN1, the protein that initiates glycogen biosynthesis, hence its name GNIP. In addition to enhancing the activity of GN1, TRIM7 has E3 ubiquitin ligase activity ( 14 ), and through this function, it participates in several processes including glycogen accumulation ( 20 ), cancer development ( 14 , 15 , 16 , 17 ), regulation of atherosclerosis ( 18 ), and of the toll-like receptor 4–mediated innate response ( 23 ). The E3 ubiquitin ligase function is also involved in the immune response against viral infections ( 20 , 21 , 22 ).…”

“…TRIM7 is also involved in osteosarcoma metastasis and chemoresistance regulation ( 17 ). Through the activation of c-Jun/AP-1 signaling pathway, TRIM7 also promotes proliferation and migration of atherosclerotic vascular smooth muscle cells ( 18 ). Moreover, TRIM7 exhibits in vitro autoubiquitination activity, which could be attributed to its RING finger/B-box domains, and promotes glycogen accumulation in skeletal muscle when overexpressed ( 19 ).…”