RESUMO
Excessive accumulation of collagen leads to fibrosis. Integrin α1ß1 (Itgα1ß1) prevents kidney fibrosis by reducing collagen production through inhibition of the EGF receptor (EGFR) that phosphorylates cytoplasmic and nuclear proteins. To elucidate how the Itgα1ß1/EGFR axis controls collagen synthesis, we analyzed the levels of nuclear tyrosine phosphorylated proteins in WT and Itgα1-null kidney cells. We show that the phosphorylation of the RNA-DNA binding protein fused in sarcoma (FUS) is higher in Itgα1-null cells. FUS contains EGFR-targeted phosphorylation sites and, in Itgα1-null cells, activated EGFR promotes FUS phosphorylation and nuclear translocation. Nuclear FUS binds to the collagen IV promoter, commencing gene transcription that is reduced by inhibiting EGFR, down-regulating FUS, or expressing FUS mutated in the EGFR-targeted phosphorylation sites. Finally, a cell-penetrating peptide that inhibits FUS nuclear translocation reduces FUS nuclear content and collagen IV transcription. Thus, EGFR-mediated FUS phosphorylation regulates FUS nuclear translocation and transcription of a major profibrotic collagen gene. Targeting FUS nuclear translocation offers a new antifibrotic therapy.
Assuntos
Núcleo Celular/metabolismo , Fibrose/metabolismo , Fosforilação/fisiologia , Proteína FUS de Ligação a RNA/metabolismo , Transdução de Sinais/fisiologia , Animais , Sequência de Bases , Linhagem Celular , Núcleo Celular/genética , Colágeno/genética , Colágeno/metabolismo , Regulação para Baixo/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Fibrose/genética , Células HEK293 , Humanos , Integrina alfa1beta1/genética , Integrina alfa1beta1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação/genética , Regiões Promotoras Genéticas/genética , Transporte Proteico/genética , Transporte Proteico/fisiologia , Proteína FUS de Ligação a RNA/genética , Transdução de Sinais/genética , Transcrição Gênica/genéticaRESUMO
We report the first multiscale, systematic field-based testing of correlations between orbital scale advanced spaceborne thermal emission and reflection radiometer visible near-infrared (VNIR)/shortwave infrared (SWIR) reflectance and thermal infrared relative emissivity and outcrop scale Raman spectroscopy, VNIR reflectance, X-ray diffraction (XRD), and laser-induced breakdown spectroscopy (LIBS) mineralogy and chemistry in a saline dry lakebed. This article is one of three reports describing the evolution of salt deposits, meteorological record, and surface and subsurface salt mineralogy in Dalangtan, Qaidam Basin, a hyperarid region of the Tibet Plateau, China, as potential environmental, mineralogical, and biogeochemical analogs to Mars. We have successfully bridged remote sensing data to fine scale mineralogy and chemistry data. We have defined spectral end-members in the northwestern Qaidam Basin and classified areas within the study area on the basis of their spectral similarity to the spectral end-members. Results of VNIR/SWIR classification reveal zonation of spectral units within three large anticlinal domes in the study area that can be correlated between the three structures. Laboratory Raman, VNIR reflectance, XRD, and LIBS data of surface mineral samples collected along a traverse over Xiaoliangshan (XLS) indicate that the surface is dominated by gypsum, Mg sulfates, Na sulfates, halite, and carbonates, with minor concentrations of illite present in most samples as well. Our results can be used as a first step toward better characterizing the potential of orbital reflectance spectroscopy as a method for mineral detection and quantification in salt-rich planetary environments, with the benefit that this technique can be validated on the ground using instruments onboard rovers.
Assuntos
Clima Desértico , Geologia , Lagos , Minerais/química , Salinidade , Imageamento Tridimensional , Tecnologia de Sensoriamento Remoto , Análise Espectral , Propriedades de Superfície , Tibet , Difração de Raios XRESUMO
Stable isotope ratios of H, C, and O are powerful indicators of a wide variety of planetary geophysical processes, and for Mars they reveal the record of loss of its atmosphere and subsequent interactions with its surface such as carbonate formation. We report in situ measurements of the isotopic ratios of D/H and (18)O/(16)O in water and (13)C/(12)C, (18)O/(16)O, (17)O/(16)O, and (13)C(18)O/(12)C(16)O in carbon dioxide, made in the martian atmosphere at Gale Crater from the Curiosity rover using the Sample Analysis at Mars (SAM)'s tunable laser spectrometer (TLS). Comparison between our measurements in the modern atmosphere and those of martian meteorites such as ALH 84001 implies that the martian reservoirs of CO2 and H2O were largely established ~4 billion years ago, but that atmospheric loss or surface interaction may be still ongoing.