rBMSCs/ITGA5B1 Promotes Human Vascular Smooth Muscle Cell Differentiation via Enhancing Nitric Oxide Production
- Author:
Yingxin ZHANG
1
;
Jie DING
;
Cong XU
;
Hongli YANG
;
Peng XIA
;
Shengjun MA
;
Haiying CHEN
Author Information
- Publication Type:Original Article
- Keywords: Bone marrow derived mesenchymal stem cells; Integrin; Nitric oxide; Phenotypic transition; Human vascular smooth muscle cell (HPASMC)
- MeSH: Activating Transcription Factor 4; Animals; Anoikis; Bone Marrow; Cell Differentiation; Endothelins; Epiregulin; Genes, Synthetic; Heme Oxygenase-1; Humans; In Vitro Techniques; Inflammation; Integrins; Mesenchymal Stromal Cells; Monocrotaline; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nitric Oxide Synthase Type III; Nitric Oxide; Oxidative Stress; Phenotype; Prostaglandin-Endoperoxide Synthases; Pulmonary Artery; Rats; Receptors, Thromboxane A2, Prostaglandin H2
- From:International Journal of Stem Cells 2018;11(2):168-176
- CountryRepublic of Korea
- Language:English
- 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.
