کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8529859 | 1558862 | 2018 | 25 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
LOX-1 mediated phenotypic switching of pulmonary arterial smooth muscle cells contributes to hypoxic pulmonary hypertension
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
In pulmonary hypertension (PH), pulmonary arterial smooth muscle cells (PASMCs) are dedifferentiated, undergoing a contractile-to-synthetic phenotypic switching. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays diverse roles in the cardiovascular system, but its contribution to PH remains to be fully defined. The present study was undertaken to explore the role of LOX-1 in PASMCs dedifferentiation in hypoxia-induced pulmonary vascular remodeling and PH. In a rat model of hypoxic PH, pulmonary vascular remodeling was accompanied by increased expression of LOX-1 in pulmonary arteries. In primary rat PASMCs, hypoxia-induced PASMCs dedifferentiation occurred concomitantly with LOX-1 upregulation. Inhibition of LOX-1 by either siRNA knockdown or neutralizing antibody significantly ameliorated PASMCs dedifferentiation. Mechanistically, LOX-1 promotes PASMCs dedifferentiation under hypoxic conditions via ERK1/2-Elk-1/MRTF-A/SRF signaling pathway. In conclusion, our data uncovers an important role of LOX-1 in the maintenance of PASMCs phenotype. Therapeutic targeting of LOX-1/ERK1/2-Elk-1/MRTF-A/SRF signaling axis would be exploited to treat hypoxic PH.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 818, 5 January 2018, Pages 84-95
Journal: European Journal of Pharmacology - Volume 818, 5 January 2018, Pages 84-95
نویسندگان
Weifang Zhang, Tiantian Zhu, Weihua Wu, Xiaoyue Ge, Xiaoming Xiong, Zheng Zhang, Changping Hu,