| 1. |
- Petkevicius, K., et al.
(författare)
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TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The regulation of cellular phosphatidylethanolamine (PE) acyl chain composition is poorly understood. Here, the authors show that TLCD1 and TLCD2 proteins mediate the formation of monounsaturated fatty acid-containing PE species and promote the progression of non-alcoholic steatohepatitis. The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.
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| 2. |
- Hammes, T. O., et al.
(författare)
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Lactobacillus rhamnosus GG reduces hepatic fibrosis in a model of chronic liver disease in rats
- 2017
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Ingår i: Nutricion Hospitalaria. - : ARAN Ediciones. - 0212-1611 .- 1699-5198. ; 34:3, s. 702-709
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Tidskriftsartikel (refereegranskat)abstract
- Background: The intestinal dysbiosis is common in chronic liver disease and can induce to inflammatory responses and mediate the collagen deposition in the liver. Aim: To evaluate the probiotic Lactobacillus rhamnosus GG (LGG) for the treatment of liver fibrosis in a model of chronic cholestatic liver disease in rats. Methods: Male adult Wistar rats (n = 29) were submitted to common bile duct ligation (BDL groups) or manipulation of common bile duct without ligation (Ctrl groups).Two weeks after surgery, each group was randomly divided to receive 1 ml of PBS (Ctrl and BDL) or PBS containing 2.5 x 10(7) CFU of LGG (Ctrl-P and BDL-P) through gavages for 14 days. Euthanasia occurred 33 days after surgery when samples of blood and liver tissue were collected. Results: The hepatic gene expression of Tlr4, Tnf alpha, IL-6, Tgf beta, and metalloproteinase-2 and -9 were higher in the BDL groups in comparison to Ctrl. The ductular reaction evaluated by immunocontent of cytokeratin-7 (CK7) and the content of collagen were increased in BDL groups. Also, there was an imbalance in the antioxidant defenses (superoxide dismutase and catalase) and an increase in the oxidative stress marker sulfhydryl in BDL groups. The treatment with LGG significantly reduced gene expression of IL-6, collagen deposition, and ductular reaction in hepatic tissue of animals from BDL-P groups. Conclusion: The treatment with the probiotic LGG was able to reduce liver fibrosis, ductular reaction, and hepatic gene expression of IL-6 in a model of cholestatic liver disease in rats.
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| 3. |
- Wilhelmsson, Ulrika, 1970, et al.
(författare)
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Nestin Regulates Neurogenesis in Mice Through Notch Signaling From Astrocytes to Neural Stem Cells
- 2019
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 29:10, s. 4050-4066
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Tidskriftsartikel (refereegranskat)abstract
- The intermediate filament (nanofilament) protein nestin is a marker of neural stem cells, but its role in neurogenesis, including adult neurogenesis, remains unclear. Here, we investigated the role of nestin in neurogenesis in adult nestin-deficient (Nes(-/-)) mice. We found that the proliferation of Nes(-/-) neural stem cells was not altered, but neurogenesis in the hippocampal dentate gyrus of Nes(-/-) mice was increased. Surprisingly, the proneurogenic effect of nestin deficiency was mediated by its function in the astrocyte niche. Through its role in Notch signaling from astrocytes to neural stem cells, nestin negatively regulates neuronal differentiation and survival; however, its expression in neural stem cells is not required for normal neurogenesis. In behavioral studies, nestin deficiency in mice did not affect associative learning but was associated with impaired long-term memory.
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