NPS2390, a Selective Calcium-sensing Receptor Antagonist Controls the Phenotypic Modulation of Hypoxic Human Pulmonary Arterial Smooth Muscle Cells by Regulating Autophagy
Identifieur interne : 000606 ( Main/Curation ); précédent : 000605; suivant : 000607NPS2390, a Selective Calcium-sensing Receptor Antagonist Controls the Phenotypic Modulation of Hypoxic Human Pulmonary Arterial Smooth Muscle Cells by Regulating Autophagy
Auteurs : Xue Peng [République populaire de Chine] ; Can Wei [République populaire de Chine] ; Hong-Zhu Li [République populaire de Chine] ; Hong-Xia Li [République populaire de Chine] ; Shu-Zhi Bai [République populaire de Chine] ; Li-Na Wang [République populaire de Chine] ; Yu-Hui Xi [République populaire de Chine] ; Jin Yan [République populaire de Chine] ; Chang-Qing Xu [République populaire de Chine]Source :
- Journal of Translational Internal Medicine [ 2450-131X ] ; 2019.
Abstract
Calcium-sensing receptor (CaSR) is known to regulate hypoxia-induced pulmonary hypertension (HPH) and vascular remodeling via the phenotypic modulation of pulmonary arterial smooth muscle cells (PASMCs) in small pulmonary arteries. Moreover, autophagy is an essential modulator of VSMC phenotype. But it is not clear whether CaSR can regulate autophagy involving the phenotypic modulation under hypoxia.
The viability of human PASMCs was detected by cell cycle and BrdU. The expressions of proliferation protein, phenotypic marker protein, and autophagy protein in human PASMCs were determined by western blot.
Our results showed that hypoxia-induced autophagy was considerable at 24 h. The addition of NPS2390 decreased the expression of autophagy protein and synthetic phenotype marker protein osteopontin and increased the expression of contractile phenotype marker protein SMA-ɑ and calponin via suppressing downstream PI3K/Akt/mTOR signal pathways.
Our study demonstrates that treatment of NPS2390 was conducive to inhibit the proliferation and reverse phenotypic modulation of PASMCs by regulating autophagy levels.
Url:
DOI: 10.2478/jtim-2019-0013
PubMed: 31380238
PubMed Central: 6661874
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PMC:6661874Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">NPS2390, a Selective Calcium-sensing Receptor Antagonist Controls the Phenotypic Modulation of Hypoxic Human Pulmonary Arterial Smooth Muscle Cells by Regulating Autophagy</title>
<author><name sortKey="Peng, Xue" sort="Peng, Xue" uniqKey="Peng X" first="Xue" last="Peng">Xue Peng</name>
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<series><title level="j">Journal of Translational Internal Medicine</title>
<idno type="ISSN">2450-131X</idno>
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<sec id="j_jtim-2019-0013_s_005"><title>Background and Objectives</title>
<p>Calcium-sensing receptor (CaSR) is known to regulate hypoxia-induced pulmonary hypertension (HPH) and vascular remodeling via the phenotypic modulation of pulmonary arterial smooth muscle cells (PASMCs) in small pulmonary arteries. Moreover, autophagy is an essential modulator of VSMC phenotype. But it is not clear whether CaSR can regulate autophagy involving the phenotypic modulation under hypoxia.</p>
</sec>
<sec id="j_jtim-2019-0013_s_006"><title>Methods</title>
<p>The viability of human PASMCs was detected by cell cycle and BrdU. The expressions of proliferation protein, phenotypic marker protein, and autophagy protein in human PASMCs were determined by western blot.</p>
</sec>
<sec id="j_jtim-2019-0013_s_007"><title>Results</title>
<p>Our results showed that hypoxia-induced autophagy was considerable at 24 h. The addition of NPS2390 decreased the expression of autophagy protein and synthetic phenotype marker protein osteopontin and increased the expression of contractile phenotype marker protein SMA-ɑ and calponin via suppressing downstream PI3K/Akt/mTOR signal pathways.</p>
</sec>
<sec id="j_jtim-2019-0013_s_008"><title>Conclusions</title>
<p>Our study demonstrates that treatment of NPS2390 was conducive to inhibit the proliferation and reverse phenotypic modulation of PASMCs by regulating autophagy levels.</p>
</sec>
</div>
</front>
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