title: Mesenchymal stem cells suppress CaN/NFAT expression in the pulmonary arteries of rats with pulmonary hypertension.
abstract: Inflammation and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) is considered the primary pathological feature of pulmonary hypertension (PH). The present study determined that mesenchymal stem cells (MSCs) suppress the expression of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT) in the pulmonary arteries of rats, and this may exert a therapeutic effect on PH. The potential therapeutic effects of MSCs on PH were assessed via the transplantation of human umbilical cord-derived MSCs, which were cultured in serum-free medium, into a monocrotaline (MCT)-induced PH rat model. Subsequently, the expression levels of tumor necrosis factor (TNF)-α in lung tissue and plasma, and of CaN and NFATc2 in pulmonary arteries were assessed. In the rat model of MCT-induced PH, investigated in the present study, TNF-α expression levels were detected in the lung tissue, and the levels of TNF-α in the plasma were increased. Furthermore, in addition to hemodynamic changes and the evident medial hypertrophy of the pulmonary muscular arterioles, CaN and NFATc2 expression levels were significantly upregulated in the pulmonary arteries. In the present study, the transplantation of MSCs, cultured in serum-free medium, decreased the levels of TNF-α in the lung tissue and plasma of rats, and downregulated CaN and NFATc2 expression in the pulmonary arteries. Furthermore, hemodynamic abnormalities and medial hypertrophy of the pulmonary muscular arterioles were notably improved. Therefore, the results of the present study may suggest that the administration of MSCs in PH may suppress the production of TNF-α, and downregulate the expression of CaN and NFATc2 in pulmonary arteries, which may provide an effective treatment for PH by suppressing the pathological proliferation of PASMCs.
authors.affiliation: Laboratory of Tissue Engineering and Stem Cells, Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China ; Department of Pediatrics, The General Hospital of Huabei Oil Field Company, Renqiu, Hebei 062552, P.R. China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: National Engineering Research Center of Cell Products, AmCellGene Co. Ltd., Tianjin 300457, P.R. China.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Han
authors.affiliation: National Engineering Research Center of Cell Products, AmCellGene Co. Ltd., Tianjin 300457, P.R. China.
authors.forename: Zhongchao
authors.initials: Z
authors.lastname: Han
authors.affiliation: Laboratory of Tissue Engineering and Stem Cells, Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Zhixu
authors.initials: Z
authors.lastname: He
keywords: calcineurin; mesenchymal stem cell; model; nuclear factor of activated T-cells; pulmonary hypertension; transplantation