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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., (© 2014 AlphaMed Press.)

Aminoacyl-tRNA synthetases (ARSs) ligate amino acids to their cognate tRNAs. It has been suggested that mammalian ARSs are linked to the EF-1 complex for efficient channeling of aminoacyl tRNAs to ribosome. Here we systemically investigated possible interactions between human ARSs and the subunits of EF-1 (alpha, beta, gamma, and delta) using a yeast two-hybrid assay. Among the 80 tested pairs, leucyl- and histidyl-tRNA synthetases were found to make strong and specific interaction with the EF-1gamma and beta while glu-proly-, glutaminyl-, alanyl-, aspartyl-, lysyl-, phenylalanyl-, glycyl-, and tryptophanyl-tRNA synthetases showed moderate interactions with the different EF-1 subunits. The interactions of leucyl- and histidyl-tRNA synthetase with the EF-1 complex were confirmed by immunoprecipitation and in vitro pull-down experiments. Interestingly, the aminoacylation activities of these two enzymes, but not other ARSs, were stimulated by the cofactor of EF-1, GTP. These data suggest that a systematic interaction network may exist between mammalian ARSs and EF-1 subunits probably to enhance the efficiency of in vivo protein synthesis., (©2002 Elsevier Science (USA).)