Hypoxia promotes cell proliferation by modulating E2F1 in chicken pulmonary arterial smooth muscle cells

Yang, Ying; Sun, Feng; Zhang, Chen; Wang, Hao; Wu, Guoyao; Wu, Zhenlong

doi:10.1186/2049-1891-4-28

Cited by 6 publications

(3 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pulmonary vascular remodeling was confirmed as an important pathological contributor to AS that leads to an increase in pulmonary vascular resistance, prolonging elevated arterial hypertension [ 24 ]. Among vascular well cells, the proliferation and hypertrophy of vascular smooth muscle cells was thought to be a main contributor that facilitates pulmonary vascular remodeling and has an important role in AS progression [ 57 , 58 ], this was in accord with the current changes in this study. Comprehensively, the pathological changes further supported the present RNA-seq findings in the pulmonary arteries from broilers with or without AS, and we revealed some specific components of complex molecular circuitry regulating pulmonary artery remodeling underlying in AS progression.…”

Section: Discussionsupporting

confidence: 83%

Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome

Yang

Xiao

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

BackgroundPulmonary arterial hypertension, also known as Ascites syndrome (AS), remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear.Methodology/Principal FindingsWe obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq) analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs) with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology) terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (Padj<0.05) regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak-STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKα, IkB, P38, five cytokines IL-6, IL8, IL-1β, IL-18, and MIP-1β. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group.Conclusions/SignificanceOur present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS progression.

show abstract

Section: Discussionsupporting

confidence: 83%

Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome

Yang

Xiao

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…This was of particular interest to us given recent reports alluding to the presence of abnormalities in the DNA repair machinery found in both pulmonary endothelial (40) and smooth muscle cells (41) from patients with IPAH. Furthermore, TopBP1 has been shown to interact with E2F1 (42), a gene reported to promote pulmonary smooth muscle cell proliferation in the setting of hypoxia (43,44). In our patient population, we found three singlenucleotide variants (SNVs) (Figure 2A) located in close proximity to both the TopBP1 transactivation domain (rs55633281) and the topoisomerase II interacting domain (rs17301766 and rs10935070) ( Figure 2B).…”

Section: Relevance Of Top Three Wes Hits To Ipah Pathobiologymentioning

confidence: 83%

Whole-Exome Sequencing Reveals TopBP1 as a Novel Gene in Idiopathic Pulmonary Arterial Hypertension

Perez

Yuan

Lyuksyutova

et al. 2014

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disorder characterized by progressive loss of pulmonary microvessels. Although mutations in the bone morphogenetic receptor 2 (BMPR2) are found in 80% of heritable and z15% of patients with IPAH, their low penetrance (z20%) suggests that other unidentified genetic modifiers are required for manifestation of the disease phenotype. Use of whole-exome sequencing (WES) has recently led to the discovery of novel susceptibility genes in heritable PAH, but whether WES can also accelerate gene discovery in IPAH remains unknown.Objectives: To determine whether WES can help identify novel gene modifiers in patients with IPAH.Methods: Exome capture and sequencing was performed on genomic DNA isolated from 12 unrelated patients with IPAH lacking BMPR2 mutations. Observed genetic variants were prioritized according to their pathogenic potential using ANNOVAR. Measurements and Main Results:A total of nine genes were identified as high-priority candidates. Our top hit was topoisomerase DNA binding II binding protein 1 (TopBP1), a gene involved in the response to DNA damage and replication stress. We found that TopBP1 expression was reduced in vascular lesions and pulmonary endothelial cells isolated from patients with IPAH. Although TopBP1 deficiency made endothelial cells susceptible to DNA damage and apoptosis in response to hydroxyurea, its restoration resulted in less DNA damage and improved cell survival.Conclusions: WES led to the discovery of TopBP1, a gene whose deficiency may increase susceptibility to small vessel loss in IPAH. We predict that use of WES will help identify gene modifiers that influence an individual's risk of developing IPAH.

show abstract

“…It has been demonstrated that hMSC at 20% O 2 exhibited significantly increased oxidative stress, DNA damage markers, and telomere shortening rates, compared with cells grown at 3% O 2 [15]. Conversely, numerous studies have demonstrated that ASCs under hypoxia showed the greater number of cells and shorter population doubling time, and oxygen tension as low as 2% had the greatest impact on cell growth [16][17][18]. For clinical applications, stem cells must be sufficiently expanded.…”

Section: Stem Cell Proliferation In Vitromentioning

confidence: 99%

Approaches for Stimulating Proliferation of Stem Cells in Vitro

Liu¹,

Li²,

Cai³

2017

JAMB

View full text Add to dashboard Cite

Abstract.With the increasing incidence rates in the complex human diseases, e.g., Alzheimer's disease, spinal cord injury, and diabetes, there exists an urgent need to search for more effective and efficient therapies. Cell-based therapy has been considered to be a novel and effective therapeutic approach for the great potential of stem cells in their self-renewal and multipotential differentiational capacity. However, a major difficulty with the success of stem cell therapy is the availability of stem cells. The most serious issue is that only a limited number of stem cells can be extracted from adult tissue due to the decreasing frequency and differentiation potential with age. In order to achieve successful cell-based therapy, extensive ex vivo proliferation of stem cells is urgently required. Therefore, approaches to stimulate proliferation of stem cells are discussed in this article.

show abstract

Hypoxia promotes cell proliferation by modulating E2F1 in chicken pulmonary arterial smooth muscle cells

Cited by 6 publications

References 29 publications

Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome

Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome

Whole-Exome Sequencing Reveals TopBP1 as a Novel Gene in Idiopathic Pulmonary Arterial Hypertension

Approaches for Stimulating Proliferation of Stem Cells in Vitro

Contact Info

Product

Resources

About