Prevention of growth arrest-induced cell death of vascular smooth muscle cells by a product of growth arrest-specific gene, gas6

AbstractWe have purified Gas6 as a growth-potentiating factor for vascular smooth muscle cells (VSMCs) [Nakano, T. et al. (1995) J. Biol. Chem. 270, 5702-57051. However, specific production of Gas6 in growth-arrested cells raises an intriguing question as to the physiological function of Gas6. In this study, we found that serum-starved VSMCs secreted some survival factors and depletion of the factors induced cell death of VSMCs. Finally, we demonstrated that cell death was prevented by the addition of Gas6, suggesting that one of the major biological activity of Gas6 is protection of growth-arrested VSMCs from death

Transcriptional dynamics of immortalized human mesenchymal stem cells during transformation

Comprehensive analysis of alterations in gene expression along with neoplastic transformation in human cells provides valuable information about the molecular mechanisms underlying transformation. To further address these questions, we performed whole transcriptome analysis to the human mesenchymal stem cell line, UE6E7T-3, which was immortalized with hTERT and human papillomavirus type 16 E6/E7 genes, in association with progress of transformation in these cells. At early stages of culture, UE6E7T-3 cells preferentially lost one copy of chromosome 13, as previously described; in addition, tumor suppressor genes, DNA repair genes, and apoptosis-activating genes were overexpressed. After the loss of chromosome 13, additional aneuploidy and genetic alterations that drove progressive transformation, were observed. At this stage, the cell line expressed oncogenes as well as genes related to anti-apoptotic functions, cell-cycle progression, and chromosome instability (CIN); these pro-tumorigenic changes were concomitant with a decrease in tumor suppressor gene expression. At later stages after prolong culture, the cells exhibited chromosome translocations, acquired anchorage-independent growth and tumorigenicity in nude mice, (sarcoma) and exhibited increased expression of genes encoding growth factor and DNA repair genes, and decreased expression of adhesion genes. In particular, glypican-5(GPC5), which encodes a cell-surface proteoglycan that might be a biomarker for sarcoma, was expressed at high levels in association with transformation. Patched (Ptc1), the cell surface receptor for hedgehog (Hh) signaling, was also significantly overexpressed and co-localized with GPC5. Knockdown of GPC5 expression decreased cell proliferation, suggesting that it plays a key role in growth in U3-DT cells (transformants derived from UE6E7T-3 cells) through the Hh signaling pathway. Thus, the UE6E7T-3 cell culture model is a useful tool for assessing the functional contribution of genes showed by expression profiling to the neoplastic transformation of human fibroblasts and human mesenchymal stem cells (hMSC)

Structural Effects on the Incident Photon-to-Current Conversion Efficiency of Zn Porphyrin Dyes on the Low-Index Planes of TiO₂

The structural effects of substrates on the incident photon-to-current conversion efficiency (IPCE) of Zn porphyrin (ZnP) dyes (ZnP-ref, YD2, and ZnPBAT) have been studied on well-defined single-crystal surfaces of rutile TiO₂ (TiO₂(111), TiO₂(100), and TiO₂(110)). IPCE of ZnP-ref depends on the structure of the substrates remarkably: TiO₂(100) < TiO₂(110) < TiO₂(111). IPCE of ZnP-ref/TiO₂(111) is 13 times as high as that of ZnP-ref/TiO₂(100) at 570 nm. YD2 and ZnPBAT also give the highest IPCE on TiO₂(111). The relative coverages of the porphyrin dyes give the following order: TiO₂(111) < TiO₂(110) < TiO₂(100). This order is opposite to that of IPCEs. The orientation of the dyes is predicted using density functional theory calculations on simplified models of TiO₂ surfaces. The highest IPCE on TiO₂(111) is attributed to the high rate of electron transfer through the space due to the fluctuation of the tilt angle of the adsorbed dyes