دورية أكاديمية
Altered gene expression in pulmonary tissue of tryptophan hydroxylase-1 knockout mice: implications for pulmonary arterial hypertension.
العنوان: | Altered gene expression in pulmonary tissue of tryptophan hydroxylase-1 knockout mice: implications for pulmonary arterial hypertension. |
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المؤلفون: | Richard B Rothman, Jean L Cadet, Christina M Dersch, Michael T McCoy, Elin Lehrmann, Kevin G Becker, Michael Bader, Natalia Alenina, Michael H Baumann |
المصدر: | PLoS ONE, Vol 6, Iss 3, p e17735 (2011) |
بيانات النشر: | Public Library of Science (PLoS), 2011. |
سنة النشر: | 2011 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | The use of fenfluramines can increase the risk of developing pulmonary arterial hypertension (PAH) in humans, but the mechanisms responsible are unresolved. A recent study reported that female mice lacking the gene for tryptophan hydroxylase-1 (Tph1(-/-) mice) were protected from PAH caused by chronic dexfenfluramine, suggesting a pivotal role for peripheral serotonin (5-HT) in the disease process. Here we tested two alternative hypotheses which might explain the lack of dexfenfluramine-induced PAH in Tph1(-/-) mice. We postulated that: 1) Tph1(-/-) mice express lower levels of pulmonary 5-HT transporter (SERT) when compared to wild-type controls, and 2) Tph1(-/-) mice display adaptive changes in the expression of non-serotonergic pulmonary genes which are implicated in PAH. SERT was measured using radioligand binding methods, whereas gene expression was measured using microarrays followed by quantitative real time PCR (qRT-PCR). Contrary to our first hypothesis, the number of pulmonary SERT sites was modestly up-regulated in female Tph1(-/-) mice. The expression of 51 distinct genes was significantly altered in the lungs of female Tph1(-/-) mice. Consistent with our second hypothesis, qRT-PCR confirmed that at least three genes implicated in the pathogenesis of PAH were markedly up-regulated: Has2, Hapln3 and Retlna. The finding that female Tph1(-/-) mice are protected from dexfenfluramine-induced PAH could be related to compensatory changes in pulmonary gene expression, in addition to reductions in peripheral 5-HT. These observations emphasize the intrinsic limitation of interpreting data from studies conducted in transgenic mice that are not fully characterized. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1932-6203 |
Relation: | http://europepmc.org/articles/PMC3064573?pdf=render; https://doaj.org/toc/1932-6203 |
DOI: | 10.1371/journal.pone.0017735 |
URL الوصول: | https://doaj.org/article/b39313865104454697e06c4fa7fb3fa5 |
رقم الأكسشن: | edsdoj.b39313865104454697e06c4fa7fb3fa5 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19326203 |
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DOI: | 10.1371/journal.pone.0017735 |