Lysophosphatidic acid increases the proliferation and migration of adiposederived stem cells via the generation of reactive oxygen species.
Mol Med Rep
; 12(4): 5203-10, 2015 Oct.
Article
in En
| MEDLINE
| ID: mdl-26134517
ABSTRACT
Phospholipid derivatives, such as lysophosphatidic acid (LPA), exhibit mitogenic effects on mesenchymal stem cells; however, the molecular mechanism underlying this stimulation has yet to be identified. The aims of the present study were as follows To evaluate the stimulatory effects of LPA on the proliferation and migration of adiposederived stem cells (ASCs); to study the association between reactive oxygen species (ROS) and LPA signaling in ASCs; and to investigate the microRNAs upregulated by LPA treatment in ASCs. The results of the present study demonstrated that LPA increased the proliferation and migration of ASCs, and acted as a mitogenic signal via extracellular signalregulated kinases 1/2 and the phosphoinositide 3kinase/Akt signaling pathways. The LPA1 receptor is highly expressed in ASCs, and pharmacological inhibition of it by Ki16425 significantly attenuated the proliferation and migration of ASCs. In addition, LPA treatment generated ROS via NADPH oxidase 4, and ROS were able to function as signaling molecules to increase the proliferation and migration of ASCs. The induction of ROS by LPA treatment also upregulated the expression of miR210. A polymerase chain reaction array assay demonstrated that the expression levels of adrenomedullin and Serpine1 were increased following treatment with LPA. Furthermore, transfection with Serpine1specific small interfering RNA attenuated the migration of ASCs. In conclusion, the present study is the first, to the best of our knowledge, to report that ROS generation and miR210 expression are associated with the LPAinduced stimulation of ASCs, and that Serpine1 mediates the LPAinduced migration of ASCs. These results further suggest that LPA may be used for ASC stimulation during stem cell expansion.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stem Cells
/
Lysophospholipids
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Cell Movement
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Adipose Tissue
/
Reactive Oxygen Species
Limits:
Humans
Language:
En
Journal:
Mol Med Rep
Year:
2015
Document type:
Article