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Functional regulation of adipose-derived stem cells by PDGF-D.
Stem Cells. 2015 Feb; 33(2):542-56.SC

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+Show Affiliations

College of Pharmacy, Yonsei University, Incheon, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25332166

Citation

Hye Kim, Ji, et al. "Functional Regulation of Adipose-derived Stem Cells By PDGF-D." Stem Cells (Dayton, Ohio), vol. 33, no. 2, 2015, pp. 542-56.
Hye Kim J, Gyu Park S, Kim WK, et al. Functional regulation of adipose-derived stem cells by PDGF-D. Stem Cells. 2015;33(2):542-56.
Hye Kim, J., Gyu Park, S., Kim, W. K., Song, S. U., & Sung, J. H. (2015). Functional regulation of adipose-derived stem cells by PDGF-D. Stem Cells (Dayton, Ohio), 33(2), 542-56. https://doi.org/10.1002/stem.1865
Hye Kim J, et al. Functional Regulation of Adipose-derived Stem Cells By PDGF-D. Stem Cells. 2015;33(2):542-56. PubMed PMID: 25332166.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional regulation of adipose-derived stem cells by PDGF-D. AU - Hye Kim,Ji, AU - Gyu Park,Sang, AU - Kim,Wang-Kyun, AU - Song,Sun U, AU - Sung,Jong-Hyuk, PY - 2014/06/27/received PY - 2014/09/09/revised PY - 2014/09/14/accepted PY - 2014/10/22/entrez PY - 2014/10/22/pubmed PY - 2015/9/17/medline KW - Adipose-derived stem cells KW - Mitochondrial ROS generation KW - Mitogenic effect KW - PDGF-D KW - Paracrine effect SP - 542 EP - 56 JF - Stem cells (Dayton, Ohio) JO - Stem Cells VL - 33 IS - 2 N2 - 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. SN - 1549-4918 UR - https://www.unboundmedicine.com/medline/citation/25332166/Functional_regulation_of_adipose_derived_stem_cells_by_PDGF_D_ L2 - https://doi.org/10.1002/stem.1865 DB - PRIME DP - Unbound Medicine ER -