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rBMSCs/ITGA5B1 Promotes Human Vascular Smooth Muscle Cell Differentiation via Enhancing Nitric Oxide Production
- Source :
- International Journal of Stem Cells
- Publication Year :
- 2018
- Publisher :
- Korean Society for Stem Cell Research, 2018.
-
Abstract
- Background and objectives Previous studies have shown that integrins alpha5beta1 (ITGA5B1) gene-modified rat bone marrow mesenchymal stem cells (rBMSCs) could prevent cell anoikis and increase the nitric oxide (NO) production. Here we examined the capability of rBMSCs/ITGA5B1 on the phenotype modulation of Human Pulmonary Artery Smooth Muscle Cell (HPASMC) in vitro. Methods and results The synthetic (dedifferentiated) phenotype of HPASMC was induced by monocrotaline (MCT, 1μM) for 24 h and then co-cultured with rBMSCs/ITGA5B1 in a transwell culture system. The activation of NO/cGMP (nitric oxide/Guanosine-3', 5'-cyclic monophosphate) signaling was investigated in HPASMC. The changes of pro-inflammatory factors, oxidative stress, vasodilator, vasoconstrictor, contractile and synthetic genes, and the morphological changes of HPASMC were investigated. The results of this study showed that the NO/cGMP signal, endothelial nitric oxide synthase (eNOS) expression, the expression of the vasoprotective genes heme oxygenase-1 (HMOX1) and prostaglandin-endoperoxide synthase 2 (PTGS2) were increased, but the expression of transforming growth factor-β1 (TGF-β1), CCAAT/enhancer-binding proteins delta (Cebpd), Kruppel-like factor 4 (KLF4), and activating transcription factor 4 (ATF4) were reduced in MCT treated HPASMC co-cultured with rBMSCs/ITGA5B1. The synthetic smooth muscle cells (SMCs) phenotype markers thrombospondin-1, epiregulin and the vasoconstrictor endothelin (ET)-1, thromboxane A2 receptor (TbxA2R) were down-regulated, whereas the contractile SMCs phenotype marker transgelin expression was up-regulated by rBMSCs/ITGA5B1. Furthermore, rBMSCs/ITGA5B1 promoted the morphological restoration from synthetic (dedifferentiation) to contractile (differentiation) phenotype in MCT treated HPASMC. Conclusions rBMSCs/ITGA5B1 could inhibit inflammation and oxidative stress related genes to promote the HPASMC cell differentiation by activation NO/cGMP signal.
- Subjects :
- Human vascular smooth muscle cell (HPASMC)
0301 basic medicine
Cellular differentiation
Cell
Integrin
Bone marrow derived mesenchymal stem cells
030204 cardiovascular system & hematology
Phenotypic transition
Nitric oxide
Thromboxane receptor
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Anoikis
Chemistry
Cell Biology
Cell biology
030104 developmental biology
medicine.anatomical_structure
KLF4
Vascular smooth muscle cell differentiation
Original Article
Endothelin receptor
Developmental Biology
Subjects
Details
- ISSN :
- 20055447
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- International Journal of Stem Cells
- Accession number :
- edsair.doi.dedup.....ec7624cbb2972ad1c2853312f95bdb18