title: Functional regulation of adipose-derived stem cells by PDGF-D.
abstract: Platelet-derived growth factor-D (PDGF-D) was recently identified, and acts as potent mitogen for mesenchymal cells. PDGF-D also induces cellular transformation and promotes tumor growth. However, the functional role of PDGF-D in adipose-derived stem cells (ASCs) has not been identified. Therefore, we primarily investigated the autocrine and paracrine roles of PDGF-D in this study. Furthermore, we identified the signaling pathways and the molecular mechanisms involved in PDGF-D-induced stimulation of ASCs. It is of interest that PDGF-B is not expressed, but PDGF-D and PDGF receptor-β are expressed in ASCs. PDGF-D showed the strongest mitogenic effect on ASCs, and PDGF-D regulates the proliferation and migration of ASCs through the PI3K/Akt pathways. PDGF-D also increases the proliferation and migration of ASCs through generation of mitochondrial reactive oxygen species (mtROS) and mitochondrial fission. mtROS generation and fission were mediated by p66Shc phosphorylation, and BCL2-related protein A1 and Serpine peptidase inhibitor, clade E, member 1 mediated the proliferation and migration of ASCs. In addition, PDGF-D upregulated the mRNA expression of diverse growth factors such as vascular endothelial growth factor A, fibroblast growth factor 1 (FGF1), FGF5, leukemia inhibitory factor, inhibin, beta A, interleukin 11, and heparin-binding EGF-like growth factor. Therefore, the preconditioning of PDGF-D enhanced the hair-regenerative potential of ASCs. PDGF-D-induced growth factor expression was attenuated by a pharmacological inhibitor of mitogen-activated protein kinase pathway. In summary, PDGF-D is highly expressed by ASCs, where it acts as a potent mitogenic factor. PDGF-D also upregulates growth factor expression in ASCs. Therefore, PDGF-D can be considered a novel ASC stimulator, and used as a preconditioning agent before ASC transplantation.
authors.affiliation: College of Pharmacy, Yonsei University, Incheon, Korea.
authors.forename: Ji
authors.initials: J
authors.lastname: Hye Kim
authors.forename: Sang
authors.initials: S
authors.lastname: Gyu Park
authors.forename: Wang-Kyun
authors.initials: WK
authors.lastname: Kim
authors.forename: Sun U
authors.initials: SU
authors.lastname: Song
authors.forename: Jong-Hyuk
authors.initials: JH
authors.lastname: Sung
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis* / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: C000595707:BCL2 protein, human; D016207:Cytokines; D008222:Lymphokines; C427493:PDGFD protein, human; D010982:Platelet-Derived Growth Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species
keywords: Adipose-derived stem cells; Mitochondrial ROS generation; Mitogenic effect; PDGF-D; Paracrine effect