RUNX3 is up-regulated in abdominal aortic aneurysm and regulates the function of vascular smooth muscle cells by regulating TGF-β1
| Autor: | Xiaowei Wang, Haimeng Zhou, Zhongxiao Zhou, Xin Zou |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Histology Vascular smooth muscle Physiology Blotting Western Enzyme-Linked Immunosorbent Assay Real-Time Polymerase Chain Reaction Transfection Muscle Smooth Vascular Transforming Growth Factor beta1 Extracellular matrix Downregulation and upregulation Cell Movement medicine.artery medicine Humans Gene silencing RNA Small Interfering Transcription factor Aorta Cells Cultured Aged Cell Proliferation Extracellular Matrix Proteins Chemistry Cell growth Cell Biology General Medicine Middle Aged digestive system diseases Up-Regulation Cell biology Core Binding Factor Alpha 3 Subunit cardiovascular system Female Aortic Aneurysm Abdominal Plasmids |
| Zdroj: | Journal of Molecular Histology. 53:1-11 |
| ISSN: | 1567-2387 1567-2379 |
| Popis: | Abdominal aortic aneurysm (AAA) has been associated with the dysfunction of vascular smooth muscle cells (VSMCs) and extracellular matrix (ECM) remodelling. Runt-related transcription factor 3 (RUNX3) has been reported to be up-regulated in aneurysmal aorta samples compared with normal aorta. However, its function in VSMCs and the mechanism of function remains unknown. Therefore, our study aimed to investigate the role of RUNX3 in ECM remodelling and VSMC function, and further explore the underlying mechanism. Our results verified that RUNX3 was increased in aortic samples of AAA compared with healthy controls. Overexpression vectors of RUNX3 (ov-RUNX3) and siRNA of RUNX3 (si-RUNX3) were transfected into Human aortic smooth muscle cells (HAoSMCs). The results indicated that ov-RUNX3 promoted cell proliferation, migration, and MMP-2/3/9 secretion, and suppressed TIMP-1, collagen I/III, SM22, MYH11 and CNN1 expression in HAoSMCs. The silencing of RUNX3 has the opposite effect. Furthermore, we found that RUNX3 targets TGF-β1 and suppressed its transcription. The silencing of TGF-β1 increased cell proliferation, migration and MMP-2/3/9 expression, and inhibited TIMP-1, Collagen I/III, SM22, MYH11 and CNN1 expression. In addition, TGF-β1 reversed the effect of RUNX3 overexpression on HAoSMCs. Hence, our study indicated that RUNX3 promotes cell proliferation, migration, and ECM remodelling through suppressing TGF-β1. |
| Databáze: | OpenAIRE |
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