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Biomed Pharmacother. 2018 Mar;99:1-8. doi: 10.1016/j.biopha.2018.01.038. Epub 2018 Jan 8.

Integrin alpha5beta1 suppresses rBMSCs anoikis and promotes nitric oxide production.

Author information

1
Central laboratory, and key laboratory of Oral and Maxillofacial-Head and Neck Medical Biology, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, China.
2
Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong, 252000, China.
3
Department of Cardiac Surgery, Provincial Hospital Affiliated to Shandong Universtity, Shandong University, Jinan, 250000, China.
4
Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong, 252000, China. Electronic address: xyz930911@163.com.
5
Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, Shandong, 252000, China; School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia. Electronic address: lwang@csu.edu.au.

Abstract

BACKGROUND:

Cell based therapy has been heralded as a novel, promising therapeutic strategy for cardiovascular diseases including pulmonary arterial hypertension (PAH). However, the low survival rate after transplantation due to cell death via anoikis is a major obstacle in stem cell therapy. Cells adhesion via Integrin alpha5beta1 (ITGA5B1) has a tendency to exert higher maximum forces. The present study aimed to evaluate the potential protective effect of ITGA5B1 on rat bone marrow mesenchymal stem cells (rBMSCs) from anoikis.

METHODS:

Mononuclear cells were isolated by density gradient centrifugation with Ficoll, and rBMSCs cell surface markers were evaluated by flow cytometry. Osteogenic and adipocyte differentiation was determined by Alizarin Red S and Oil Red O staining respectively. The expression of Integrin A5 (ITGA5), Integrin B1 (ITGB1), eNOS and actived-caspase-3 mRNA or protein was confirmed by qPCR and western-blot. Cell adhesion, cell viability, anoikis and the migration of rBMSCs were also evaluated. Nitric oxide (NO) production was detected by the greiss assay.

RESULTS:

Co-infected with Integrin A5 and B1 lentivirus to rBMSCs increased ITGA5 and ITGB1 mRNA and protein expression. ITGA5B1 enhanced the cell adhesion, cell viability, cell migration and NO production but reduced the cell anoikis in rBMSCs/ITGA5B1 groups.

CONCLUSION:

Transduction of rat rBMSCs with ITGA5B1 lentivirus could prevent cell anoikis and increase NO production.

KEYWORDS:

Anoikis; Bone marrow derived mesenchymal stem cells; Integrin; Nitric oxide; Pulmonary arterial hypertension

PMID:
29324307
DOI:
10.1016/j.biopha.2018.01.038
[Indexed for MEDLINE]

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