Adipose-derived mesenchymal stromal cells improve hemodynamic function in pulmonary arterial hypertension: identification of microRNAs implicated in modulating endothelial function

Autor: Jun Li, Pengbo Wang, Zhiyuan Tang, Shuwen Zhang, Fulu Dong, Lin Luo, Caixin Zhang, Songshi Ni
Rok vydání: 2019
Předmět:
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
MAPK/ERK pathway
Cancer Research
Cell Survival
Immunology
Adipose tissue
Apoptosis
Pulmonary Artery
Mesenchymal Stem Cell Transplantation
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
VEGF Signaling Pathway
Animals
Humans
Immunology and Allergy
Medicine
Endothelium
Genetics (clinical)
Cell Proliferation
Pulmonary Arterial Hypertension
Transplantation
Monocrotaline
business.industry
Hemodynamics
Wnt signaling pathway
Endothelial Cells
Mesenchymal Stem Cells
Cell Biology
Actin cytoskeleton
Coculture Techniques
Vascular endothelial growth factor
Disease Models
Animal
MicroRNAs
Gene Ontology
030104 developmental biology
Adipose Tissue
Oncology
chemistry
030220 oncology & carcinogenesis
Cancer research
Hypertrophy
Left Ventricular
Signal transduction
business
Signal Transduction
Zdroj: Cytotherapy. 21:416-427
ISSN: 1465-3249
DOI: 10.1016/j.jcyt.2019.02.011
Popis: Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial endothelial hyperproliferation and dysfunction. Restoration of endothelial function is a common goal of available treatments. In the present study, human adipose-derived mesenchymal stromal cells (ASCs) were co-cultured with monocrotaline pyrrole-treated human pulmonary arterial endothelial cells (HPAECs); increased proliferation of HPAECs and expression of vascular endothelial growth factor (VEGF) were observed. High throughput sequencing results showed that six microRNAs (miMNAs) of ASCs were significantly dysregulated. In monocrotaline-induced PAH rat models, ASC transplantation improved the right ventricle systolic pressure, right ventricle hypertrophy and pulmonary endothelium hyperproliferation, and four of the six miRNAs were validated in the lung tissue samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these dysregulated miRNAs were involved in the regulation of transcription, signal transduction, negative regulation of cell proliferation through mitogen-activated protein kinase (MAPK) signaling pathway, Wnt signaling pathway, VEGF signaling pathway, cytokine-cytokine receptor interaction, regulation of actin cytoskeleton, transforming growth factor (TGF)-beta signaling pathway and P53 signaling pathway. Our data indicates that the unique six miRNA expression signature could be involved in the PAH endothelial repair by ASCs.
Databáze: OpenAIRE
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