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rBMSCs/ITGA5B1 Promotes Human Vascular Smooth Muscle Cell Differentiation via Enhancing Nitric Oxide Production
International Journal of Stem Cells ; : 168-176, 2018.
Article in English | WPRIM | ID: wpr-739930
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), Krüppel-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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Phenotype / Pulmonary Artery / Bone Marrow / In Vitro Techniques / Integrins / Cell Differentiation / Endothelins / Monocrotaline / Prostaglandin-Endoperoxide Synthases / Oxidative Stress Limits: Animals / Humans Language: English Journal: International Journal of Stem Cells Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phenotype / Pulmonary Artery / Bone Marrow / In Vitro Techniques / Integrins / Cell Differentiation / Endothelins / Monocrotaline / Prostaglandin-Endoperoxide Synthases / Oxidative Stress Limits: Animals / Humans Language: English Journal: International Journal of Stem Cells Year: 2018 Type: Article