Platelet‐derived growth factor‐BB (PDGF‐BB) induces differentiation of bone marrow endothelial progenitor cell‐derived cell line TR‐BME2 into mural cells, and changes the phenotype

Abstract

Blood vessels are composed of endothelial cells (EC) and mural cells, and the interaction between EC and mural cells is essential for the development and maintenance of the vasculature. EC differentiate from bone marrow-derived endothelial progenitor cells (EPC). Recently, we established a conditionally immortalized bone marrow EPC-derived cell line, TR-BME2, and a brain capillary EC (BCEC) line, TR-BBB, from temperature-sensitive-SV40 T-antigen gene transgenic rats. To understand the function of EPC, it is important to analyze the difference between EPC and mature EC such as BCEC. In this study, we identified EPC-specific genes by means of subtractive hybridization between TR-BME2 and TR-BBB. There was no significant difference between TR-BME2 and TR-BBB in the mRNA level of annexin II, which is expressed in EC. In contrast, the mRNA level of smooth muscle cell (SMC) markers such as smooth muscle protein 22 (SM22), calvasculin, and platelet-derived growth factor (PDGF) receptor-beta, was higher in TR-BME2 than in TR-BBB. Moreover, the mRNA level of contractile SMC markers, such as smooth muscle alpha-actin and SM22, was increased in the absence of EC growth factors, such as vascular endothelial growth factor. The mRNA level of synthetic SMC markers, such as matrix Gla protein, was increased by the addition of PDGF-BB. The SMC derived from TR-BME2 showed an altered phenotype, from contractile-type to synthetic-type, when they were cultured in the absence of PDGF-BB. These results show that TR-BME2 cells have higher levels of SMC markers compared with mature EC, and can differentiate into contractile- or synthetic-type SMC.

Splicing of HDAC7 modulates the SRF-myocardin complex during stem-cell differentiation towards smooth muscle cells

“…Recent reports indicate that vascular progenitor cells are able to differentiate into contractile-type SMCs in the absence of VEGF or into synthetictype SMCs in the presence of PDGF-BB, respectively (Miyata et al, 2005). However, reports have also shown that treatment of…”

Sp1-dependent Activation of HDAC7 Is Required for Platelet-derived Growth Factor-BB-induced Smooth Muscle Cell Differentiation from Stem Cells

“…Platelet-derived growth factor-BB (PDGF-BB) has been identified as one of the key modulators for SMC differentiation from stem/progenitor cells (1,10,11) and mature vascular SMC phenotype modulation (12,13). Our previous experiments showed that SMC differentiation from ES cells was enhanced through short stimulations with PDGF-BB (within 24 h) in the absence of serum, indicating that the duration of serum deprivation and the proliferation stage of cells are important parameters in SMC differentiation mediated by PDGF-BB (7).…”

Stem Cells and Transplant Arteriosclerosis

“…It was also observed that mesenchymal stem cells can differentiate into both ECs and SMCs 72 and that vascular progenitor cells are able to differentiate into contractile-type smooth muscles in the absence of VEGF or into synthetic-type phenotypes in the presence of PDGF-BB, respectively. 117 In addition, immune suppression drug cyclosporine can inhibit both endothelial and smooth muscle progenitor cell growth and thus influences neointimal formation in transplant models. 118 In human embryonic stem cells, a report demonstrated that a population of vascular progenitors with the ability to differentiate into endothelial-like and smooth muscle-like cells has been identified.…”