Lysophosphatidic acid increases the proliferation and migration of adipose-derived stem cells via the generation of reactive oxygen species

Sangjin Kang, Juhee Han, Seung Yong Song, Won Serk Kim, Soyoung Shin, Ji Hye Kim, Hyosun Ahn, Jin Hyun Jeong, Sung Joo Hwang, Jong Hyuk Sung

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 adipose-derived 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 signal-regulated kinases 1/2 and the phosphoinositide 3-kinase/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 miR-210. A polymerase chain reaction array assay demonstrated that the expression levels of adrenomedullin and Serpine1 were increased following treatment with LPA. Furthermore, transfection with Serpine1-specific 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 miR-210 expression are associated with the LPA-induced stimulation of ASCs, and that Serpine1 mediates the LPA-induced migration of ASCs. These results further suggest that LPA may be used for ASC stimulation during stem cell expansion.

Original languageEnglish
Pages (from-to)5203-5210
Number of pages8
JournalMolecular Medicine Reports
Volume12
Issue number4
DOIs
Publication statusPublished - 2015 Oct 1

Fingerprint

Stem cells
Reactive Oxygen Species
Stem Cells
lysophosphatidic acid
Lysophosphatidic Acid Receptors
Adrenomedullin
1-Phosphatidylinositol 4-Kinase
Mitogen-Activated Protein Kinase 3
NADPH Oxidase
Mitogen-Activated Protein Kinase 1
Polymerase chain reaction
MicroRNAs
Mesenchymal Stromal Cells
Phosphatidylinositols
Small Interfering RNA
Transfection
Phospholipids
Assays
Phosphotransferases
Pharmacology

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

Cite this

Kang, Sangjin ; Han, Juhee ; Song, Seung Yong ; Kim, Won Serk ; Shin, Soyoung ; Kim, Ji Hye ; Ahn, Hyosun ; Jeong, Jin Hyun ; Hwang, Sung Joo ; Sung, Jong Hyuk. / Lysophosphatidic acid increases the proliferation and migration of adipose-derived stem cells via the generation of reactive oxygen species. In: Molecular Medicine Reports. 2015 ; Vol. 12, No. 4. pp. 5203-5210.
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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 adipose-derived 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 signal-regulated kinases 1/2 and the phosphoinositide 3-kinase/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 miR-210. A polymerase chain reaction array assay demonstrated that the expression levels of adrenomedullin and Serpine1 were increased following treatment with LPA. Furthermore, transfection with Serpine1-specific 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 miR-210 expression are associated with the LPA-induced stimulation of ASCs, and that Serpine1 mediates the LPA-induced migration of ASCs. These results further suggest that LPA may be used for ASC stimulation during stem cell expansion.",
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Lysophosphatidic acid increases the proliferation and migration of adipose-derived stem cells via the generation of reactive oxygen species. / Kang, Sangjin; Han, Juhee; Song, Seung Yong; Kim, Won Serk; Shin, Soyoung; Kim, Ji Hye; Ahn, Hyosun; Jeong, Jin Hyun; Hwang, Sung Joo; Sung, Jong Hyuk.

In: Molecular Medicine Reports, Vol. 12, No. 4, 01.10.2015, p. 5203-5210.

Research output: Contribution to journalArticle

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T1 - Lysophosphatidic acid increases the proliferation and migration of adipose-derived stem cells via the generation of reactive oxygen species

AU - Kang, Sangjin

AU - Han, Juhee

AU - Song, Seung Yong

AU - Kim, Won Serk

AU - Shin, Soyoung

AU - Kim, Ji Hye

AU - Ahn, Hyosun

AU - Jeong, Jin Hyun

AU - Hwang, Sung Joo

AU - Sung, Jong Hyuk

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N2 - 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 adipose-derived 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 signal-regulated kinases 1/2 and the phosphoinositide 3-kinase/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 miR-210. A polymerase chain reaction array assay demonstrated that the expression levels of adrenomedullin and Serpine1 were increased following treatment with LPA. Furthermore, transfection with Serpine1-specific 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 miR-210 expression are associated with the LPA-induced stimulation of ASCs, and that Serpine1 mediates the LPA-induced migration of ASCs. These results further suggest that LPA may be used for ASC stimulation during stem cell expansion.

AB - 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 adipose-derived 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 signal-regulated kinases 1/2 and the phosphoinositide 3-kinase/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 miR-210. A polymerase chain reaction array assay demonstrated that the expression levels of adrenomedullin and Serpine1 were increased following treatment with LPA. Furthermore, transfection with Serpine1-specific 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 miR-210 expression are associated with the LPA-induced stimulation of ASCs, and that Serpine1 mediates the LPA-induced migration of ASCs. These results further suggest that LPA may be used for ASC stimulation during stem cell expansion.

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