scholarly journals Hypoxia-inducible factor-2 alpha promotes the proliferation of human placenta-derived mesenchymal stem cells through the MAPK/ERK signaling pathway

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Chengxing Zhu ◽  
Jiong Yu ◽  
Qiaoling Pan ◽  
Jinfeng Yang ◽  
Guangshu Hao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Human Placenta ◽  
Hypoxia Inducible Factor ◽  
Erk Signaling

scholarly journals Mesenchymal Stem Cells Activate the MEK/ERK Signaling Pathway and Enhance DNA Methylation via DNMT1 in PBMC from Systemic Lupus Erythematosus

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Hui Xiong ◽  
Zhixuan Guo ◽  
Zengqi Tang ◽  
Xuechen Ai ◽  
Qing Qi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Erk Signaling ◽  
Control Group ◽  
Systemic Lupus

The defective MEK/ERK signaling pathway and downstream hypomethylation pattern of lymphocytes are crucial for the pathogenesis of systemic lupus erythematosus (SLE). However, the role that the mesenchymal stem cells play in the MEK/ERK signaling pathway and DNA methylation of peripheral blood mononuclear cells (PBMC) from SLE patients remains unknown. In this study, we found that the MEK/ERK signaling pathway of PBMC from SLE patients was activated after the coculture with bone marrow-derived mesenchymal stem cells (BM-MSC) compared with that from the control group. In addition, the expression level of DNA methyltransferase 1 (DNMT1) increased while the levels of CD70, integrin, alpha L (ITGAL), selectin-l, and IL-13 were reduced in PBMC from SLE patients. However, no obvious effect of BM-MSC on PBMC from healthy controls was observed. These findings revealed that BM-MSC might downregulate the expression of methylation-sensitive genes and then suppress the autoactivated PBMC via the MEK/ERK signaling pathway. And it may be one of the mechanisms that BM-MSC ameliorated SLE.

scholarly journals hCTLA4-Gene-Modified Human Bone Marrow-Derived Mesenchymal Stem Cells (hBMMSCs) Maintain POSTN Secretion to Enhance the Migration Capability of Allogeneic hBMMSCs through the Integrin αvβ3/FAK/ERK Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Lei Song ◽  
Fei Zhang ◽  
Rui Zhou ◽  
Jun Xiao ◽  
Lei He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Culture Supernatant ◽  
Recombinant Adenovirus ◽  
Negative Control ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Erk Signaling

Cytotoxic T-lymphocyte-associated protein 4- (CTLA4-) modified human bone marrow-derived mesenchymal stem cells (hBMMSCs) might be promising seed cells for bone tissue engineering. However, the underlying mechanism is not clear. In the present study, we investigated whether CTLA4-modified hBMMSCs are involved in the migration of allogeneic hBMMSCs (allo-hBMMSCs) by maintaining POSTN secretion. hBMMSCs were isolated from different groups, named hBMMSCs and allo-hBMMSCs. hBMMSCs that were infected with the negative control (NC), empty adenovirus- or recombinant adenovirus-expressing CTLA4, POSTN, or CTLA4 plus the shRNA of POSTN were named NC hBMMSCs, CTLA4-modified hBMMSCs, POSTN-modified hBMMSCs, or CTLA4+shPOSTN-modified hBMMSCs, respectively. They were then cocultured with PBMCs in a 1 : 5 ratio with 2.5 μg/mL phytohemagglutinin (PHA). The coculture supernatant was collected to treat allo-hBMMSCs with anti-integrin αvβ3 IgG, or negative control IgG, as a control. Following this, ELISA, Transwell assays, wound healing assays, and western blotting were performed. We found that the POSTN level was higher in the culture supernatant of CTLA4- and POSTN-modified hBMMSCs than in NC hBMMSCs cocultured with PBMCs treated with PHA. The migration capability of allo-hBMMSCs was enhanced, and the integrin αvβ3/FAK/ERK signaling pathway in allo-hBMMSCs was activated by the culture supernatant of CTLA4- and POSTN-modified hBMMSCs cocultured with PBMCs treated with PHA. Additionally, these induced effects can be weakened by POSTN knockdown, and the migration capability of allo-hBMMSCs was blocked by anti-integrin αvβ3 IgG. In conclusion, hCTLA4-gene-modified hBMMSCs maintain POSTN secretion to enhance the migration capability of allogeneic hBMMSCs through the integrin αvβ3/FAK/ERK signaling pathway in the T cell immune activation environment.

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