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Pulmonary hypertension (PH) is a rare and severe progressive disease. It results from hypertrophic remodeling of distal pulmonary arterioles that increases pulmonary arterial pressure and pulmonary vascular resistance in the absence of left heart, pulmonary parenchymal, or thromboembolic disease. Hypoxia-inducible factor-1 (HIF-1) regulates a large number of genes related to the occurrence and development of PH, and induces pulmonary angiogenesis, cell proliferation and migration, cellular energy metabolism and utilization. HIF-1 is an important component of the pathogenesis of hypoxic PH and plays an important role in driving the pathological process of pulmonary vascular and right ventricular remodeling. This article systematically elucidated the role and regulation of HIF-1 in hypoxic PH and its potential in targeted therapy of PH.
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Aim To explore the role and mechanism of nuclear receptor subfamily 1,group D,member 1(NR1D1)in the proliferation and migration of mouse adventitial fibroblasts(AFs). Methods Primary AFs isolated from C57BL/6J mice were cultured. Adenovirus carrying Nr1d1 gene was used to overexpress NR1D1 in AFs. The expression of β-catenin was restored by SKL2001. Proliferating cell nuclear antigen(Ki-67)immunofluorescence staining and CCK-8 staining were used to determine cell proliferation,and scratch test was used to determine cell migration. qPCR was used to determine the mRNA level of Nr1d1. Western blot was used to determine the protein levels of NR1D1 and β-catenin. To investigate the role of NR1D1 in intimal hyperplasia,20 male wild type C57BL/6J mice were randomly divided into sham group,carotid artery endothelial injury,sham+SR9009(NR1D1 agonist)group and carotid artery endothelial injury+SR9009(n=5 in each group). They were treated with DMSO or SR9009(100 mg·kg-1·d-1)via intraperitoneal injection for 14 days after operation,respectively. The degree of carotid intimal hyperplasia was measured by HE staining 28 days after operation. Results NR1D1 overexpression significantly reduced the percentage of Ki-67-positive cells(P<0.01),total cell number(P<0.01)and slowed down the rate of wound-healing(P<0.01). NR1D1 overexpression significantly inhibited the expression of β-catenin(P<0.05). After the expression of β-catenin was restored by SKL2001,the inhibitory effects of NR1D1 overexpression on the proliferation and migration of AFs were abolished(P<0.01). Enhanced activity of NR1D1 significantly ameliorated intimal hyperplasia after carotid endothelial injury(P<0.01). Conclusion NR1D1 may inhibit the proliferation and migration of AFs via suppressing the expression of β-catenin.
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Objective:To study interferon alpha (IFN-α) inhibition of proliferation and apoptosis induction of human brain vascular adventitial fibroblasts(HBVAFs)via IFI16.Methods:Cultured HBVAFs were treated with transfection IFI16 siRNA and/or IFN-α in vitro instantaneously.The protein and mRNA levels of IFI16,P53,P21 were measured by Western blot and Real-time PCR.MTT was used to detect the cell proliferation of the HBVAFs.Cell cycle and apoptosis were analyzed by flow cytometry.Results:IFN-α with terminal concentration of 2 000-5 000 kU/L induce significantly expression of IFI16 in HBVAFs,without any significant difference.Stimulated with 2 000 kU/L IFN-α up-regulated the expression of P53,P21 at protein and mRNA levels,and inhibited the cell proliferation and promote cells apoptosis in HBVAFs.Such effect was restrained by transfection with IFI16 siRNA into HBVAFs.Conclusion:IFN-α inhibits HBVAFs proliferation and induces apoptosis may partly relate to the increased IFI16 expression.
ABSTRACT
Transforming growth factor β (TGF-β) is a growth factor regulating cell proliferation, differentiation and the production of extracellular matrix. Vascular remodeling is a common pathological process of many cardiovascular diseases. TGF-β can accelerate vascular adventitial fibroblasts proliferation, induce the transdifferentiation of vascular adventitial fibroblasts into myofibroblasts, and promote the vascular remodeling and a series of changes in vascular injury sites. Smad proteins involved in TGF-β intracellular signal transduction can regulate the expression of TGF-β target gene by binding with differenot proteins, so as to perform multiple biological functions. This review introduces the influence of TGF-β on the proliferation, migration and phenotype traasformation of vascular adventitial fibroblasts. © 2006 Editorial office of Foreign Medical Sciences.
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Objective To investigate the effects of pioglitazone on angiotensin Ⅱ(AngⅡ) -induced proliferation and collagen typeⅠ expression of adventitial fibroblasts (AF). Methods The AFs were isolated from rat thoracic aorta. MTT colorimetry and flow cytometry were used to study the effects of pioglitazone on proliferation and cell cycles of AF. The expression of collagen typeⅠ regulated by pioglitazone was examined by the method of Western blot. Results Pioglitazone inhibited the proliferation of AF in a dose-dependent manner, and the most marked effect could be observed at the concentration of 10?10-6 mol/L for pioglitazone (P