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-b 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. STEM CELLS 2015;33:542-556

Ginsenoside Rg1 and platelet-rich fibrin enhance human breast adipose-derived stem cells function for soft tissue regeneration

“…Moreover, hypoxia increases ASCs proliferation through HIF-1α activation [38], and VEGF stimulates ASCs growth VEGF [39]. Both Hye and Gehmert found that PDGF pretreatment of ASCs before transplantation increased neovascularization [40–41]. We found that HIF-1α and VEGF protein and mRNA levels were increased by treatment with G-Rg1, PRF.…”

Differences in the neovascular potential of thymus versus subcutaneous adipose‐derived stem cells from patients with myocardial ischaemia

“…Previous studies have confirmed the involvement of the CD140b receptor in the generation of mitochondrial ROS (Hye Kim, Gyu Park, Kim, Song, & Sung, ), the CD184 receptor in the chemotactic effects of SDF1α on human ASCs subjected to hypoxia (Thangarajah et al, ) and the CD271 receptor in the immunomodulatory properties of mesenchymal stem cells (Kuçi et al, ). Thus, we subsequently quantified the percentage of ASCs expressing these receptors.…”

From Type I to Type II: Design, Synthesis, and Characterization of Potent Pyrazin‐2‐ones as DFG‐Out Inhibitors of PDGFRβ

“…According to the proposed type I binding mode for CP‐673451, different incubation times had no significant effect on PDGFRβ kinase activity (IC 50 values: 0 min=7 n m , 60 min=8 n m , 120 min=11 n m ). Thus, in line with earlier reports, these data provide further evidence for CP‐673451 being a type I inhibitor . In contrast, compound 5 blocking PDGFRβ activity was determined to be considerably time dependent (IC 50 values: 0 min=143 n m , 10 min=60 n m , 120 min=20 n m ).…”

“…Thus, in line with earlier reports,t hese data provide furthere vidence for CP-673451 being at ype Ii nhibitor. [55] In contrast, compound 5 blocking PDGFRb activity was determined to be considerably time dependent (IC 50 values: 0min = 143 nm,1 0min = 60 nm,1 20 min = 20 nm). In fact, over ap eriod of 120 min, the IC 50 values of 5 weres hifted by af actor of seven toward higherP DGFRb affinity.T hese re- Figure 6.…”