title: Lysophosphatidic acid increases the proliferation and migration of adipose‑derived stem cells via the generation of reactive oxygen species.
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.
authors.affiliation: Department of Applied Bioscience, CHA University, Pocheon, Gyeonggi 487-010, Republic of Korea.
authors.forename: Sangjin
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Applied Bioscience, CHA University, Pocheon, Gyeonggi 487-010, Republic of Korea.
authors.forename: Juhee
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Plastic and Reconstructive Surgery, Yonsei University College of Medicine, Seoul 120-749, Republic of Korea.
authors.forename: Seung Yong
authors.initials: SY
authors.lastname: Song
authors.affiliation: Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Won-Serk
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Shin
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Yonsei University, Incheon 406‑840, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Yonsei University, Incheon 406‑840, Republic of Korea.
authors.forename: Hyosun
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Yonsei University, Incheon 406‑840, Republic of Korea.
authors.forename: Jin-Hyun
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Yonsei University, Incheon 406‑840, Republic of Korea.
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Hwang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Yonsei University, Incheon 406‑840, Republic of Korea.
authors.forename: Jong-Hyuk
authors.initials: JH
authors.lastname: Sung
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D053607:Adrenomedullin / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: C507862:ADM protein, human; D008246:Lysophospholipids; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D017382:Reactive Oxygen Species; D049368:Receptors, Lysophosphatidic Acid; C051321:SERPINE1 protein, human; D053607:Adrenomedullin; C032881:lysophosphatidic acid