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Combination treatment of adipose-derived stem cells and adiponectin attenuates pulmonary arterial hypertension in rats by inhibiting pulmonary arterial smooth muscle cell proliferation and regulating the AMPK/BMP/Smad pathway
- Source :
- International Journal of Molecular Medicine
- Publication Year :
- 2017
- Publisher :
- D.A. Spandidos, 2017.
-
Abstract
- The present study aimed to assess the effects of therapy with adiponectin (APN) gene-modified adipose-derived stem cells (ADSCs) on pulmonary arterial hypertension (PAH) in rats and the underlying cellular and molecular mechanisms. ADSCs were successfully isolated from the rats and characterized. ADSCs were effectively infected with the green fluorescent protein (GFP)-empty (ADSCs-V) or the APN-GFP (ADSCs-APN) lentivirus and the APN expression was evaluated by ELISA. Sprague-Dawley rats were administered monocrotaline (MCT) to develop PAH. The rats were treated with MCT, ADSCs, ADSCs-V and ADSCs-APN. Then ADSCs-APN in the lung were investigated by confocal laser scanning microscopy and western blot analysis. Engrafted ADSCs in the lung were located around the vessels. Mean pulmonary arterial pressure (mPAP) and the right ventricular hypertrophy index (RVHI) in the ADSCs-APN-treated mice were significantly decreased as compared with the ADSCs and ADSCs-V treatments. Pulmonary vascular remodeling was assessed. Right ventricular (RV) function was evaluated by echocardiography. We found that pulmonary vascular remodeling and the parameters of RV function were extensively improved after ADSCs-APN treatment when compared with ADSCs and ADSCs-V treatment. Pulmonary artery smooth muscle cells (PASMCs) were isolated from the PAH rats. The antiproliferative effect of APN on PASMCs was assayed by Cell Counting Kit-8. The influence of APN and specific inhibitors on the levels of bone morphogenetic protein (BMP), adenosine monophosphate activated protein kinase (AMPK), and small mothers against decapentaplegia (Smad) pathways was detected by western blot analysis. We found that APN suppressed the proliferation of PASMCs isolated from the PAH rats by regulating the AMPK/BMP/Smad pathway. This effect was weakened by addition of the AMPK inhibitor (compound C) and BMP2 inhibitor (noggin). Therefore, combination treatment with ADSCs and APN effectively attenuated PAH in rats by inhibiting PASMC proliferation and regulating the AMPK/BMP/Smad pathway.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
animal structures
Hypertension, Pulmonary
Cell
Myocytes, Smooth Muscle
Adipose tissue
Bone Morphogenetic Protein 2
Smad Proteins
SMAD
Pulmonary Artery
03 medical and health sciences
AMP-Activated Protein Kinase Kinases
Internal medicine
pulmonary arterial hypertension
Genetics
medicine
Adipocytes
Animals
Humans
AMPK/BMP/Smad pathway
Cell Proliferation
Adiponectin
adiponectin
Cell growth
business.industry
pulmonary arterial smooth muscle cells
Lentivirus
AMPK
General Medicine
Genetic Therapy
Articles
Cell cycle
gene therapy
Rats
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Adipose Tissue
Apoptosis
adipose-derived stem cells
business
Corrigendum
Protein Kinases
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1791244X and 11073756
- Volume :
- 41
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Medicine
- Accession number :
- edsair.doi.dedup.....a53fe8e86c308248d8291d9995d2fc69