Functional regulation of adipose-derived stem cells by PDGF-D

Ji Hye Kim, Sang Gyu Park, Wang Kyun Kim, Sun U. Song, Jong Hyuk Sung

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)542-556
Number of pages15
JournalStem Cells
Volume33
Issue number2
DOIs
Publication statusPublished - 2015 Feb 1

Fingerprint

Platelet-Derived Growth Factor
Stem Cells
Platelet-Derived Growth Factor Receptors
Intercellular Signaling Peptides and Proteins
Reactive Oxygen Species
Mitochondrial Dynamics
Interleukin-11
Leukemia Inhibitory Factor
Fibroblast Growth Factor 1
Stem Cell Transplantation
Mitogen-Activated Protein Kinases
Protease Inhibitors
Phosphatidylinositol 3-Kinases
Mitogens
Vascular Endothelial Growth Factor A
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Hye Kim, Ji ; Gyu Park, Sang ; Kim, Wang Kyun ; Song, Sun U. ; Sung, Jong Hyuk. / Functional regulation of adipose-derived stem cells by PDGF-D. In: Stem Cells. 2015 ; Vol. 33, No. 2. pp. 542-556.
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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.",
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Hye Kim, J, Gyu Park, S, Kim, WK, Song, SU & Sung, JH 2015, 'Functional regulation of adipose-derived stem cells by PDGF-D', Stem Cells, vol. 33, no. 2, pp. 542-556. https://doi.org/10.1002/stem.1865

Functional regulation of adipose-derived stem cells by PDGF-D. / Hye Kim, Ji; Gyu Park, Sang; Kim, Wang Kyun; Song, Sun U.; Sung, Jong Hyuk.

In: Stem Cells, Vol. 33, No. 2, 01.02.2015, p. 542-556.

Research output: Contribution to journalArticle

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