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Reduced C1q/Tumor Necrosis Factor-Related Protein9 Expression Promotes Hcy-Induced VSMCs Migration via Negative Regulating Endoplasmic Reticulum Stress |Biomedgrid

Journal: American Journal of Biomedical Science & Research (Vol.19, No. 1)

Publication Date:

Authors : ; ; ; ;

Page : 33-38

Keywords : C1q/Tumor Necrosis Factor-Related Protein9; Endoplasmic Reticulum Stress; Hcy; VSMCs Migration; DNA Methyltransferase1;

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Abstract

To provide a theoretical basis for the prevention and treatment of hyperhomocysteinemia (HHcy), the current study aimed to investigate the mechanism underlying the effect of homocysteine (Hcy) on inducing the migration of vascular smooth muscle cells (VSMCs) via inhibited C1q/Tumor necrosis factor-related protein9 (CTRP9) expression negative regulating endoplasmic reticulum stress (ERs). Therefore, the overexpression and interference plasmid of CRRP9 were constructed, transfected into VSMCs cells, and administered Hcy stimulation cells. At the same time, endoplasmic reticulum stress inhibitor (4-PBA) and endoplasmic reticulum stress activator (TM) intervention cells were administered. The migration ability of VSMCs at 0h and 48h was assessed by wound-healing assays. The protein expression of CTRP9, DNA methyltransferase 1 (DNMT1), ERs marker GRP78 and AFT6a in VSMCs were detected by western blot. Furthermore, DNMT1 inhibitor 5-Azc was given to intervene cells to observe the effect of DNMT1 on CTRP9 expression. The results show that Hcy can down-regulate CTRP9 protein expression and stimulate VSMCs migration. Overexpression of CTRP9 can delay VSMCs migration caused by Hcy. Meanwhile, activation of ERs simultaneously with overexpression of CTRP9 can inhibit VSMCs migration. Interference with CTRP9 has achieved the opposite results. It is suggested that CTRP9 down-regulation promotes Hcy induced VSMCs migration, and ERs plays an important role in this process. In terms of mechanism, interference CTRP9 can activate ERs, while overexpression of CTRP9 can inhibit ERs. Meanwhile, the expression of DNMT1 is up-regulated by Hcy, and the expression of CTRP9 can be up-regulated by inhibiting DNMT1. In summary, the results of this study suggest that reduced C1q/Tumor necrosis factor-related protein9 expression promotes Hcy-induced VSMCs migration via negative regulating endoplasmic reticulum stress. The up regulation of DNMT1 expression induced by Hcy plays an important role in this process, and CTRP9 may be regulated by methylation.

Last modified: 2024-11-18 22:02:48