The promoting role of Cx43 on the proliferation and migration of arterial smooth muscle cells for angiotensin II-dependent hypertension
| Autor: | Li Li, Ai-Mei Zhang, Zi-Ting Dang, Tian Tian, Qihua Jia, Nan Cao, Ke-Tao Ma, Xue-Chun Tang, Rui-Juan Gao, Jun-qiang Si, Jingrong Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
MAPK/ERK pathway medicine.medical_specialty Vascular smooth muscle Myocytes Smooth Muscle Muscle Smooth Vascular Internal medicine medicine Animals Pharmacology (medical) Osteopontin Protein kinase C Cell Proliferation Angiotensin II receptor type 1 biology Chemistry Kinase Angiotensin II Biochemistry (medical) Angiotensin-converting enzyme Rats Endocrinology Connexin 43 Hypertension cardiovascular system biology.protein sense organs biological phenomena cell phenomena and immunity |
| Zdroj: | Pulmonary pharmacologytherapeutics. 70 |
| ISSN: | 1522-9629 |
| Popis: | Background Recent studies have shown that endothelin-1 and angiotensin II (AngII) can increase gap junctional intercellular communication (GJIC) by activating Mitogen-activated protein kinases (MAPKs) pathway. However, not only the precise interaction of AngII with Connexin43(Cx43) and the associated functions remain unclear, but also the regulatory role of Cx43 on the AngII-mediated promotion proliferation and migration of VSMCs is poorly understood. Material and methods Our research applicated pressure myography measurements, immunofluorescence and Western blot analyses to investigate the changes in physiological indicators in spontaneously hypertensive rats (SHRs) and AngII-stimulated proliferation and migration of A7r5 SMCs(Rat vascular smooth muscle cells). The aim was to elucidate the role of CX43 in hypertension induced by AngII. Results Chronic ramipril (angiotensin converting enzyme inhibitor) management for SHRs significantly attenuated blood pressure and blood vessel wall thickness, also reduced contraction rate in the cerebral artery. The cerebral artery contraction rates, mRNA and protein expression of Cx43, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) protein expression in the SHR + ramipril and SHR + ramipril + carbenoxolone (CBX, Cx43 specific blocker) groups were significantly lower than those in the SHR group. Cx43 protein expression and Ser368 phosphorylated Cx43 protein levels increased significantly in AngII-stimulated A7r5 cells. However, the levels of phosphorylated Cx43 decreased after pre-treatment with candesartan (AT1 receptor blocker), GF109203X (protein kinase C (PKC) blocker) and U0126 (mitogen-activated protein kinases/extracellular signal-regulated kinase1/2(MEK/ERK1/2)-specific blocker) in AngII-stimulated A7r5 cells. Cx43 was widely distributed in the cell membrane, nucleus, and cytoplasm of the SMCs. Furthermore, pre-treatment of the AngII- stimulated A7r5 cells with Gap26 (Cx43 blocker) significantly inhibited cell migration and decreased the expression levels of MEK1/2, ERK1/2, P-MEK1/2, and P-ERK1/2. Conclusion Our research confirms that Cx43 plays an important role in the regulation of proliferation and migration of VSMCs via MEK/ERK and PKC signal pathway in AngII-dependent hypertension. |
| Databáze: | OpenAIRE |
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