Regulation of heparin-binding EGF-like growth factor expression by phorbol ester in a human hepatoma-derived cell line

AbstractHeparin-binding EGF-like growth factor (HB-EGF) is a recently identified potent mitogen for smooth muscle cells and fibroblasts. HB-EGF has been shown to be an EGF receptor ligand, and also to stimulate epithelial cell growth. A human hepatoma-derived cell line, Mahlavu, was analyzed for the production of HB-EGF mRNA and active HB-EGF protein. It was found that the cell line synthesized very low or undetectable basal level of HB-EGF mRNA. However, the addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) led to a rapid and transient rise in HB-EGF mRNA level. HB-EGF in Mahlavu cells appears to be regulated by a protein kinase C (PKC) pathway, since PKC inhibitors, H7, staurosporin, and calphostin C, abrogated the induction of HB-EGF mRNA by TPA. Unlike vascular smooth muscle cells, induction of HB-EGF gene transcription by TPA was blocked completely by incubation with cycloheximide, suggesting that protein synthesis may be a prerequisite for HB-EGF gene transcription in Mahlavu cells. Mahlavu cells were also found to release a bioactive HB-EGF-like protein into conditioned medium which stimulates DNA synthesis in EP170.7 cells. This activity was neutralized by an anti-HB-EGF antibody. These results indicate that HB-EGF gene transcription is regulated via a PKC pathway, resulting in secretion of active HB-EGF into the culture medium of hepatoma-derived Mahlavu cells

Detection of the Far-infrared [O III] and Dust Emission in a Galaxy at Redshift 8.312: Early Metal Enrichment in the Heart of the Reionization Era

We present the Atacama Large Millimeter/submillimeter Array (ALMA) detection of the [O III] 88 $\mu$m line and rest-frame 90 $\mu$m dust continuum emission in a Y-dropout Lyman break galaxy (LBG), MACS0416_Y1, lying behind the Frontier Field cluster MACS J0416.1-2403. This [O III] detection confirms the LBG with a spectroscopic redshift of $z = 8.3118 \pm 0.0003$, making this object one of the furthest galaxies ever identified spectroscopically. The observed 850 $\mu$m flux density of $137 \pm 26$ $\mu$Jy corresponds to a de-lensed total infrared (IR) luminosity of $L_{\rm IR} = (1.7 \pm 0.3) \times 10^{11} L_{\odot}$ if assuming a dust temperature of $T_{\rm dust} = 50$ K and an emissivity index of $\beta = 1.5$, yielding a large dust mass of $4 \times 10^6 M_{\odot}$. The ultraviolet-to-far IR spectral energy distribution modeling where the [O III] emissivity model is incorporated suggests the presence of a young ($\tau_{\rm age} \approx 4$ Myr), star-forming (SFR $\approx 60 M_{\odot}$ yr$^{-1}$), moderately metal-polluted ($Z \approx 0.2 Z_{\odot}$) stellar component with a mass of $M_{\rm star} = 3 \times 10^8 M_{\odot}$. An analytic dust mass evolution model with a single episode of star-formation does not reproduce the metallicity and dust mass in $\tau_{\rm age} \approx 4$ Myr, suggesting a pre-existing evolved stellar component with $M_{\rm star} \sim 3 \times 10^9 M_{\odot}$ and $\tau_{\rm age} \sim 0.3$ Gyr as the origin of the dust mass.Comment: Accepted by ApJ. 18 pages, 10 figures, 5 table