ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation
| العنوان: | ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation |
|---|---|
| المؤلفون: | Lian-Wang Guo, Lynn Marcho, Craig K. Kent, Xiujie Xie, Matthew S. Stratton, Go Urabe |
| المصدر: | iScience iScience, Vol 19, Iss, Pp 872-882 (2019) |
| بيانات النشر: | Elsevier BV, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, MAPK/ERK pathway, Vascular smooth muscle, Intimal hyperplasia, Aldehyde dehydrogenase, 02 engineering and technology, Vascular Remodeling, Pathophysiology, Article, 03 medical and health sciences, Downregulation and upregulation, medicine, lcsh:Science, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, Multidisciplinary, biology, Chemistry, 021001 nanoscience & nanotechnology, medicine.disease, 3. Good health, Cell biology, 030104 developmental biology, biology.protein, lcsh:Q, Molecular Mechanism of Behavior, 0210 nano-technology, Platelet-derived growth factor receptor |
| الوصف: | Summary Vascular smooth muscle cell (VSMC) proliferation promotes intimal hyperplasia (IH) in occluding vascular diseases. Here we identified a positive role of ALDH1A3 (an aldehyde dehydrogenase) in this pro-IH process. The expression of ALDH1A3, but not that of 18 other isoforms of the ALDH family, was substantially increased in cytokine-stimulated VSMCs. PDGF(BB) stimulated VSMC total ALDH activity and proliferation, whereas ALDH1A3 silencing abolished this effect. ALDH1A3 silencing also diminished the expression of two matricellular proteins (TNC1 and ESM1), revealing a previously unrecognized ALDH1A3 function. Loss-of-function experiments demonstrated that TNC1 and ESM1 mediated ALDH1A3's pro-proliferative function via activation of AKT/mTOR and/or MEK/ERK pathways. Furthermore, ALDH inhibition with disulfiram blocked VSMC proliferation/migration in vitro and decreased TNC1 and ESM1 and IH in angioplasty-injured rat carotid arteries. Thus, ALDH1A3 promotes VSMC proliferation at least partially through TNC1/ESM1 upregulation; dampening excessive ALDH1A3 activity represents a potential approach to IH mitigation. Graphical Abstract Highlights • The ALDH1A3 isoform promotes vascular smooth muscle cell proliferation • ALDH1A3's function is mediated by its upregulation of TNC1 and ESM1 • The pan-ALDH inhibitor drug disulfiram mitigates intimal hyperplasia Pathophysiology; Vascular Remodeling; Molecular Biology; Molecular Mechanism of Behavior |
| تدمد: | 2589-0042 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3906784d31e5e69bb4b409d001b536c9 https://doi.org/10.1016/j.isci.2019.08.044 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3906784d31e5e69bb4b409d001b536c9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 25890042 |
|---|