Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Substantial involvement of TRPM7 inhibition in the therapeutic effect of Ophiocordyceps sinensis on pulmonary hypertension.

ABSTRACT: Ophiocordyceps sinensis (OCS), an entomopathogenic fungus, is known to exert antiproliferative and antitissue remodeling effects. Vascular remodeling and vasoconstriction play critical roles in the development of pulmonary hypertension (PH). The therapeutic potential of OCS for PH was investigated using rodent PH models, and cultured pulmonary artery endothelial and smooth muscle cells (PAECs and PASMCs), with a focus on the involvement of TRPM7. OCS ameliorated the development of PH, right ventricular hypertrophy and dysfunction in the monocrotaline-induced PH rats. The genetic knockout of TRPM7 attenuated the development of PH in mice with monocrotaline pyrrole-induced PH. TRPM7 was associated with medial hypertrophy and the plexiform lesions in rats and humans with PH. OCS suppressed proliferation of PASMCs derived from the PH patients. Ethanol extracts of OCS inhibited TRPM7-like current, TGF-β2-induced endothelial-mesenchymal transition, IL-6-induced STAT3 phosphorylation, and PDGF-induced Akt phosphorylation in PAECs or PASMCs. These inhibitory effects were recapitulated by either siRNA-mediated TRPM7 knockdown or treatment with TRPM7 antagonist FTY-720. OCS and FTY-720 induced vasorelaxation in the isolated normal human pulmonary artery. As a result, the present study proposes the therapeutic potential of OCS for the treatment of PH. The inhibition of TRPM7 is suggested to underlie the therapeutic effect of OCS.

SUBMITTER: Hiraishi K

PROVIDER: S-EPMC9225677 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

TRPM7 channel inhibition exacerbates pulmonary arterial hypertension through MEK/ERK pathway.

Project description:The increased proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) drive the progression of pulmonary arterial hypertension (PAH). The transient receptor potential melastatin 7 (TRPM7) is an endogenous magnesium channel reported to promote the proliferation of SMCs. However, whether TRPM7 is associated with PAH pathogenesis remains uncharacterized. We found that TRPM7 was downregulated in PASMCs from PAH human and Sprague-Dawley rats with hypoxia-induced PAH. Similar results were reproduced in PASMCs treated with PAH stimuli in vitro. Additionally, the TRPM7 currents and intracellular magnesium level in PASMCs were also reduced by PAH stimuli. Functionally, TRPM7 inhibition with waixenicin A or knockdown promoted, and reversely, its overexpression inhibited the proliferation and apoptosis resistance of PASMCs. Moreover, waixenicin A exacerbated hypoxia-induced PAH features in rats. Furthermore, TRPM7 inhibition activated MEK/ERK pathway, and the effects of TRPM7 inhibition were drastically attenuated by pathway specific inhibitor U0126, thus suggesting that activating MEK/ERK pathway is a predominant mechanism through which TRPM7 inhibition exacerbates PAH. In summary, these results may identify TRPM7 as a novel negative regulator in PAH pathogenesis, and suggest that improving its function may represent an antagonistic strategy to modify PAH progression.

| S-EPMC6629001 | biostudies-literature

Potential of the TRPM7 channel as a novel therapeutic target for pulmonary arterial hypertension.

Project description:Pulmonary arterial hypertension (PAH) is an intractable vascular disease characterized by a progressive increase in pulmonary vascular resistance caused by pulmonary vascular remodeling, which ultimately leads to right-sided heart failure. PAH remains incurable, despite the development of PAH-targeted therapeutics centered on pulmonary artery relaxants. It is necessary to identify the target molecules that contribute to pulmonary artery remodeling. Transient receptor potential (TRP) channels have been suggested to modulate pulmonary artery remodeling. Our study focused on the transient receptor potential ion channel subfamily M, member 7, or the TRPM7 channel, which modulates endothelial-to-mesenchymal transition and smooth muscle proliferation in the pulmonary artery. In this review, we summarize the role and expression profile of TRPM7 channels in PAH progression and discuss TRPM7 channels as possible therapeutic targets. In addition, we discuss the therapeutic effect of a Chinese herbal medicine, Ophiocordyceps sinensis (OCS), on PAH progression, which partly involves TRPM7 inhibition.

| S-EPMC9364263 | biostudies-literature

Ophiocordyceps sinensis raw sequence reads

Project description:Chinese cordyceps is of particular interest for its confined distribution, mysterious lifecycle, ecological importance and developmental biology. The large scale artificial cultivation of this fungus has been succeeded in China until recently but with low efficiency and high cost being ascribed to too much unsolved biological issues, such as gene expression during development and the sexuality reproduction. The success of artificial cultivation provides the convenient for sampling during the different development stages.

2019-05-14 | GSE123085 | GEO

Effect of PPARγ inhibition on pulmonary endothelial cell gene expression: Gene profiling in pulmonary hypertension

Project description:The loss of PPARγ is found to be associated with the development of pulmonary hypertension (PH). We hypothesize that PPARγ inhibition induced gene expression changes may underscore the endothelial dysfunction in the disease process. We utilized microarray analysis to determine gene expression changes in PPARγ inhibited ovine PAECs. Ovine PAECs were treated with vehicle (DMSO) or GW9662 (5μM) for 24hrs, and total RNA was extracted for microarray analysis.

2009-12-27 | E-GEOD-14546 | biostudies-arrayexpress

Genome sequencing and analysis of fungus Hirsutella sinensis isolated from Ophiocordyceps sinensis.

Project description:Ophiocordyceps sinensis has been used as a traditional medicine or healthy food in China for thousands of years. Hirsutella sinensis was reported as the only correct anamorph of O. sinensis. It is reported that the laboratory-grown H. sinensis mycelium has similar clinical efficacy and less associated toxicity compared to the wild O. sinensis. The research of the H. sinensis is becoming more and more important and urgent. To gain deeper insight into the biological and pharmacological mechanisms, we sequenced the genome of H. sinensis. The genome of H. sinensis (102.72 Mb) was obtained for the first time, with > 99% coverage. 10,200 protein-encoding genes were predicted based on the genome sequence. A detailed secondary metabolism analysis and structure verification of the main ingredients were performed, and the biosynthesis pathways of seven ingredients (mannitol, cordycepin, purine nucleotides, pyrimidine nucleotides, unsaturated fatty acid, cordyceps polysaccharide and sphingolipid) were predicted and drawn. Furthermore, infection process and mechanism of H. sinensis were studied and elaborated in this article. The enzymes involved in the infection mechanism were also predicted, cloned and expressed to verify the mechanism. The genes and proteins were predicted and annotated based on the genome sequence. The pathways of several active components in H. sinensis were predicted and key enzymes were confirmed. The work presented here would improve the understanding of the genetic basis of this organism, and contribute to further research, production and application of H. sinensis.

| S-EPMC7270455 | biostudies-literature

Effect of HNRNPA2B1 inhibition in pulmonary arterial smooth muscle cell from pulmonary arterial hypertension

Project description:Investigate the effect of HNRNPA2B1 inhibition of the transcriptomic profile of PAH-PASMC

2023-01-27 | GSE207101 | GEO

Pulmonary artery involvement in Takayasu's arteritis: diagnosis before pulmonary hypertension.

Project description:BACKGROUND:This study was performed to analyze the clinical manifestations, imaging features, and prognosis of Takayasu's arteritis (TA) with pulmonary arteritis (PA). METHODS:In total, 51 of 815 patients with TA were diagnosed with PA at the Peking Union Medical College Hospital from 1986 to 2015. The patients' medical records and radiographic data were retrospectively reviewed. RESULTS:The patients comprised 39 women and 12 men with a median age of 33 years (range, 14-67 years). The most common symptoms were dyspnea (70.6%), cough (66.7%), hemoptysis (47.1%), and chest pain (45.1%). Computed tomography (CT) pulmonary angiography, pulmonary arteriography, and pulmonary perfusion imaging showed pulmonary artery stenosis or occlusion in 44 patients. A total of 82.4% of patients had lung parenchyma lesions on CT scans, indirectly indicating pulmonary artery involvement. Additionally, 58.8% of patients had pulmonary hypertension (PH) by echocardiography. Compared with the PH group, the non-PH group was characterized by a shorter disease duration; more symptoms such as fever, chest pain, and hemoptysis; an increased erythrocyte sedimentation rate; and a higher incidence of subpleural wedge-shaped shadows on chest CT (P < 0.05). The median follow-up period was 48 months (range, 1-212 months), and all three deaths occurred in the PH group. CONCLUSIONS:The clinical manifestations of TA with PA are nonspecific. PH often complicates PA and is associated with a poor prognosis. Early clinical manifestations such as repeated fever, chest pain, hemoptysis, and recurrence of subpleural wedge-shaped shadows on chest CT should arouse suspicion of PA in patients with TA and prompt further investigations. This may allow PA to be diagnosed before the occurrence of PH. TRIAL REGISTRATION:ClinicalTrials, NCT03189602. Date of registration: June 16, 2017. Retrospectively registered.

| S-EPMC6881988 | biostudies-literature

Complete mitochondrial genome of the medicinal fungus Ophiocordyceps sinensis.

Project description:As part of a genome sequencing project for Ophiocordyceps sinensis, strain 1229, a complete mitochondrial (mt) genome was assembled as a single circular dsDNA of 157,510?bp, one of the largest reported for fungi. Conserved genes including the large and small rRNA subunits, 27 tRNA and 15 protein-coding genes, were identified. In addition, 58 non-conserved open reading frames (ncORFs) in the intergenic and intronic regions were also identified. Transcription analyses using RNA-Seq validated the expression of most conserved genes and ncORFs. Fifty-two introns (groups I and II) were found within conserved genes, accounting for 68.5% of the genome. Thirty-two homing endonucleases (HEs) with motif patterns LAGLIDADG (21) and GIY-YIG (11) were identified in group I introns. The ncORFs found in group II introns mostly encoded reverse transcriptases (RTs). As in other hypocrealean fungi, gene contents and order were found to be conserved in the mt genome of O. sinensis, but the genome size was enlarged by longer intergenic regions and numerous introns. Intergenic and intronic regions were composed of abundant repetitive sequences usually associated with mobile elements. It is likely that intronic ncORFs, which encode RTs and HEs, may have contributed to the enlarged mt genome of O. sinensis.

| S-EPMC4570212 | biostudies-literature

Effect of PPARγ inhibition on pulmonary endothelial cell gene expression: Gene profiling in pulmonary hypertension

2009-12-28 | GSE14546 | GEO

Transcriptome sequencing and analysis of the entomopathogenic fungus Hirsutella sinensis isolated from Ophiocordyceps sinensis.

Project description:BackgroundOphiocordyceps sinensis, a worm and fungus combined mixture which Hirsutella sinensis is parasitic on the caterpillar body, has been used as a traditional medicine or healthy food in China for thousands of years. H. sinensis is reported as the only correct anamorph of O. sinensis and its main active ingredients are similar to the natural O. sinensis.ResultsH. sinensis L0106, asexual strain of O. sinensis, was isolated and identified in this study. Three transcriptomes of H. sinensis at different cultivation periods (growth period 3d, pre-stable period 6d and stable period 9d) were sequenced for the first time by RNA-Seq method, and 25,511 unigenes (3d), 25,214 unigenes (6d) and 16,245 unigenes (9d) were assembled and obtained, respectively. These unigenes of the three samples were further assembled into 20,822 unigenes (All), and 62.3 percent of unigenes (All) could be annotated based on protein databases. Subsequently, the genes and enzymes involved in the biosynthesis of the active ingredients according to the sequencing and annotation results were predicted. Based on the predictions, we further investigated the interaction of different pathway networks and the corresponding enzymes. Furthermore, the differentially expressed genes (DEGs) of H. sinensis grown during different developmental stages (3d-VS-6d, 3d-VS-9d and 6d-VS-9d) were globally detected and analyzed based on the data from RNA-Seq, and 764 DEGs between 3d and 6d, 1,869 DEGs between 3d and 9d, and 770 DEGs between 6d and 9d were found, respectively.ConclusionsThis work presented here would aid in understanding and carrying out future studies on the genetic basis of H. sinensis and contribute to the further artificial production and application of this organism. This study provided a substantial contribution and basis to further characterize the gene expression profiles of H. sinensis in the metabolic pathways of active ingredients.

| S-EPMC4342880 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data