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Protective effect of hydrogen sulfide on monocrotaline-induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition
Endothelial-to-mesenchymal transition (EndMT) serves an important role in the vascular remodeling of pulmonary arterial hypertension (PAH). However, little is known about the correlation between hydrogen sulfide (H(2)S), a protective gaseous mediator in PAH and the process of EndMT. Male Sprague-Daw...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844600/ https://www.ncbi.nlm.nih.gov/pubmed/31573044 http://dx.doi.org/10.3892/ijmm.2019.4359 |
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author | Zhang, Hui Lin, Yanjun Ma, Yiwen Zhang, Junfeng Wang, Changqian Zhang, Huili |
author_facet | Zhang, Hui Lin, Yanjun Ma, Yiwen Zhang, Junfeng Wang, Changqian Zhang, Huili |
author_sort | Zhang, Hui |
collection | PubMed |
description | Endothelial-to-mesenchymal transition (EndMT) serves an important role in the vascular remodeling of pulmonary arterial hypertension (PAH). However, little is known about the correlation between hydrogen sulfide (H(2)S), a protective gaseous mediator in PAH and the process of EndMT. Male Sprague-Dawley rats (10 weeks old) received a single dose of monocrotaline (MCT; i.p., 60 mg/kg) and were randomly treated with NaHS [an H(2)S donor; intraperitoneal (i.p.) 1 mg/kg/day], DL-propagylglycine (an inhibitor of H(2)S synthesis; PAG; i.p., 10 mg/kg/day) or saline, 7 days after MCT injection. Rats were sacrificed 21 days after MCT injection. A selection of human pulmonary artery endothelial cells (HPAECs) were pretreated with NaHS or saline and stimulated with transforming growth factor (TGF)-β1 (10 ng/ml), and the other HPAECs were transfected with a cystathionine γ-lyase (CSE, an H(2)S synthesizing enzyme) plasmid and subsequently stimulated with TGF-β1. NaHS was indicated to inhibit EndMT and PAH progression by inhibiting the induction of the nuclear factor (NF)-κB-Snail pathway. In contrast, the depletion of H(2)S formation by PAG exacerbated EndMT and PAH by activating NF-κB-Snail molecules. In HPAECs, NaHS dose-dependently inhibited TGF-β1-induced EndMT and the activation of the NF-κB-Snail pathway. Transfection with a CSE plasmid significantly repressed TGF-β1-induced expression of the mesenchymal marker and upregulated the expression of the endothelial marker, which was accompanied by the suppression of the NF-κB-Snail pathway. The inhibitory effect of CSE overexpression on TGF-β1-induced EndMT was significantly reversed by pretreatment with PAG. In conclusion, the current study provides novel information elucidating the beneficial effect of H(2)S on PAH through inhibiting the induction of the NF-κB-Snail pathway and the subsequent process of EndMT in pulmonary arteries. |
format | Online Article Text |
id | pubmed-6844600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-68446002019-11-13 Protective effect of hydrogen sulfide on monocrotaline-induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition Zhang, Hui Lin, Yanjun Ma, Yiwen Zhang, Junfeng Wang, Changqian Zhang, Huili Int J Mol Med Articles Endothelial-to-mesenchymal transition (EndMT) serves an important role in the vascular remodeling of pulmonary arterial hypertension (PAH). However, little is known about the correlation between hydrogen sulfide (H(2)S), a protective gaseous mediator in PAH and the process of EndMT. Male Sprague-Dawley rats (10 weeks old) received a single dose of monocrotaline (MCT; i.p., 60 mg/kg) and were randomly treated with NaHS [an H(2)S donor; intraperitoneal (i.p.) 1 mg/kg/day], DL-propagylglycine (an inhibitor of H(2)S synthesis; PAG; i.p., 10 mg/kg/day) or saline, 7 days after MCT injection. Rats were sacrificed 21 days after MCT injection. A selection of human pulmonary artery endothelial cells (HPAECs) were pretreated with NaHS or saline and stimulated with transforming growth factor (TGF)-β1 (10 ng/ml), and the other HPAECs were transfected with a cystathionine γ-lyase (CSE, an H(2)S synthesizing enzyme) plasmid and subsequently stimulated with TGF-β1. NaHS was indicated to inhibit EndMT and PAH progression by inhibiting the induction of the nuclear factor (NF)-κB-Snail pathway. In contrast, the depletion of H(2)S formation by PAG exacerbated EndMT and PAH by activating NF-κB-Snail molecules. In HPAECs, NaHS dose-dependently inhibited TGF-β1-induced EndMT and the activation of the NF-κB-Snail pathway. Transfection with a CSE plasmid significantly repressed TGF-β1-induced expression of the mesenchymal marker and upregulated the expression of the endothelial marker, which was accompanied by the suppression of the NF-κB-Snail pathway. The inhibitory effect of CSE overexpression on TGF-β1-induced EndMT was significantly reversed by pretreatment with PAG. In conclusion, the current study provides novel information elucidating the beneficial effect of H(2)S on PAH through inhibiting the induction of the NF-κB-Snail pathway and the subsequent process of EndMT in pulmonary arteries. D.A. Spandidos 2019-12 2019-10-01 /pmc/articles/PMC6844600/ /pubmed/31573044 http://dx.doi.org/10.3892/ijmm.2019.4359 Text en Copyright: © Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Zhang, Hui Lin, Yanjun Ma, Yiwen Zhang, Junfeng Wang, Changqian Zhang, Huili Protective effect of hydrogen sulfide on monocrotaline-induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition |
title | Protective effect of hydrogen sulfide on monocrotaline-induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition |
title_full | Protective effect of hydrogen sulfide on monocrotaline-induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition |
title_fullStr | Protective effect of hydrogen sulfide on monocrotaline-induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition |
title_full_unstemmed | Protective effect of hydrogen sulfide on monocrotaline-induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition |
title_short | Protective effect of hydrogen sulfide on monocrotaline-induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition |
title_sort | protective effect of hydrogen sulfide on monocrotaline-induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844600/ https://www.ncbi.nlm.nih.gov/pubmed/31573044 http://dx.doi.org/10.3892/ijmm.2019.4359 |
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