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Research articles

ScienceAsia 50 (2024):ID 2024095 1-11 |doi: 10.2306/scienceasia1513-1874.2024.095


miR-218-5p regulates the phenotypic transformation of vascular smooth muscle cells in rat intracranial aneurysms by targeting HMGB1


Jie Penga, JieQiong Lib,*

 
ABSTRACT:     To explore the potential biological effects of miR-218-5p targeting high-mobility group protein B1 (HMGB1) mediating the phenotypic transformation of vascular smooth muscle cells (VSMCs) in intracranial aneurysm (IA) rats, an IA rat model was established, and the lentivirus vector miR-218-5p agomir or shRNA-HMBG1 was given to IA rats. The elastic fibers of the aneurysm were analyzed by Victoria Blue staining. Real-time PCR analyzed miR-218- 5p, HMGB1, and phenotypic markers (?-SMA, SM-22?, MMP2, OPN). Western blot analysis of HMGB1, SM-22?, and OPN was also performed. miR-218-5p mimics and/or HMBG1 overexpression vectors were transfected into VSMCs. The effects of miR-218-5p on cell proliferation and migration were detected by EdU method and scratch method. Dual luciferase reporter gene assay verified the targeting relationship between miR-218-5p and HMGB1. The fibers of IA rats were broken, the elastic fibers were reduced, miR-218-5p was down-regulated, and HMGB1 was up-regulated. Treatment with miR-218-5p agomir and sh-HMGB1 protected tissue elastic fiber breakage induced by IA, upregulated ?SMA and SM-22?, and down-regulated HMGB1, OPN, and MMP2. Elevating miR-218-5p inhibited VSMC proliferation and migration, increased SM-22?, and decreased OPN expression. Upregulating HMGB1 had the opposite effect. The upregulation of HMGB1 expression counteracts the inhibitory impact of miR-218-5p overexpression on the proliferative, migratory, and phenotypic transformation capacities of VSMCs. By downregulating HMGB1, miR-218-5p mediates the phenotypic transformation of VSMCs in IA rats, providing a certain research basis for further research on clinical prevention and treatment of IA.

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a Department of Neurosurgery, The First Hospital of Changsha (The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University), Changsha, Hunan 410005 China
b Department of Pediatrics, The First Hospital of Changsha (The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University), Changsha, Hunan 410005 China

* Corresponding author, E-mail: lijieqiong0812@hotmail.com

Received 21 Sep 2023, Accepted 27 May 2024