ABSTRACT
Currently potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) and NASH-related pathopoiesis have failed to achieve expected therapeutic efficacy due to the complexity of the pathogenic mechanisms. Here we show Tripartite motif containing 26 (TRIM26) as a critical endogenous suppressor of CCAAT/enhancer binding protein delta (C/EBPδ), and we also confirm that TRIM26 is an C/EBPδ-interacting partner protein that catalyses the ubiquitination degradation of C/EBPδ in hepatocytes. Hepatocyte-specific loss of Trim26 disrupts liver metabolic homeostasis, followed by glucose metabolic disorder, lipid accumulation, increased hepatic inflammation, and fibrosis, and dramatically facilitates NASH-related phenotype progression. Inversely, transgenic Trim26 overexpression attenuates the NASH-associated phenotype in a rodent or rabbit model. We provide mechanistic evidence that, in response to metabolic insults, TRIM26 directly interacts with C/EBPδ and promotes its ubiquitin proteasome degradation. Taken together, our present findings identify TRIM26 as a key suppressor over the course of NASH development.
Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Rabbits , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/prevention & control , Signal Transduction , Ubiquitination , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
Zr alloy cladding materials is the core component of the nuclear reactor, the safety of cladding materials is very important. Zr alloy cladding materials is inclined to react with water under high temperature. The products are ZrO2 and H2. The mechanical property of Zr alloy decreases promptly. In order to protect Zr alloy from high temperature water, FeCrAl thin film layer was deposited on Zr alloy surface. The structure, chemical composition, surface elemental valence and morphology of FeCrAl thin film layer were carefully investigated by XRD, EDS, XPS, and SEM. After the test of corrosion experiment, deposition of FeCrAl thin film layer on Zr alloy surface showed the better corrosion property than Zr alloy under high temperature water steam atmosphere. The corrosion rate of Zr alloy with deposited FeCrAl thin film was 1.5 times lower than that of Zr alloy. The deposition of FeCrAl thin film layer on Zr alloy is an efficient approach to improve the corrosion property.
