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Acute Liver Injury after CCl(4) Administration Is Independent of Smad7 Expression in Myeloid Cells

Myeloid cells are essential for the initiation and termination of innate and adaptive immunity that create homeostasis in the liver. Smad7 is an inhibitor of the transforming growth factor β (TGF-β) signaling pathway, which regulates inflammatory cellular processes. Knockdown of Smad7 in hepatocytes...

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Autores principales: Endig, Jessica, Unrau, Ludmilla, Sprezyna, Paulina, Rading, Sebasting, Karsak, Meliha, Goltz, Diane, Heukamp, Lukas C., Tiegs, Gisa, Diehl, Linda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888233/
https://www.ncbi.nlm.nih.gov/pubmed/31698731
http://dx.doi.org/10.3390/ijms20225528
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author Endig, Jessica
Unrau, Ludmilla
Sprezyna, Paulina
Rading, Sebasting
Karsak, Meliha
Goltz, Diane
Heukamp, Lukas C.
Tiegs, Gisa
Diehl, Linda
author_facet Endig, Jessica
Unrau, Ludmilla
Sprezyna, Paulina
Rading, Sebasting
Karsak, Meliha
Goltz, Diane
Heukamp, Lukas C.
Tiegs, Gisa
Diehl, Linda
author_sort Endig, Jessica
collection PubMed
description Myeloid cells are essential for the initiation and termination of innate and adaptive immunity that create homeostasis in the liver. Smad7 is an inhibitor of the transforming growth factor β (TGF-β) signaling pathway, which regulates inflammatory cellular processes. Knockdown of Smad7 in hepatocytes has been shown to promote liver fibrosis, but little is known about the effects of Smad7 in myeloid cells during inflammatory responses in the liver. Using mice with a myeloid-specific knockdown of Smad7 (LysM-Cre Smad7(fl/fl)), we investigated the impact of Smad7 deficiency in myeloid cells on liver inflammation and regeneration using the well-established model of CCl(4)-mediated liver injury. Early (24/48 h) and late (7 d) time points were analyzed. We found that CCl(4) induces severe liver injury, with elevated serum ALT levels, centrilobular and periportal necrosis, infiltrating myeloid cells and an increase of inflammatory cytokines in the liver. Furthermore, as expected, inflammation peaked at 24 h and subsided after 7 d. However, the knockdown of Smad7 in myeloid cells did not affect any of the investigated parameters in the CCl(4)-treated animals. In summary, our results suggest that the inhibition of TGF-β signaling via Smad7 expression in myeloid cells is dispensable for the induction and control of acute CCl(4)-induced liver injury.
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spelling pubmed-68882332019-12-09 Acute Liver Injury after CCl(4) Administration Is Independent of Smad7 Expression in Myeloid Cells Endig, Jessica Unrau, Ludmilla Sprezyna, Paulina Rading, Sebasting Karsak, Meliha Goltz, Diane Heukamp, Lukas C. Tiegs, Gisa Diehl, Linda Int J Mol Sci Article Myeloid cells are essential for the initiation and termination of innate and adaptive immunity that create homeostasis in the liver. Smad7 is an inhibitor of the transforming growth factor β (TGF-β) signaling pathway, which regulates inflammatory cellular processes. Knockdown of Smad7 in hepatocytes has been shown to promote liver fibrosis, but little is known about the effects of Smad7 in myeloid cells during inflammatory responses in the liver. Using mice with a myeloid-specific knockdown of Smad7 (LysM-Cre Smad7(fl/fl)), we investigated the impact of Smad7 deficiency in myeloid cells on liver inflammation and regeneration using the well-established model of CCl(4)-mediated liver injury. Early (24/48 h) and late (7 d) time points were analyzed. We found that CCl(4) induces severe liver injury, with elevated serum ALT levels, centrilobular and periportal necrosis, infiltrating myeloid cells and an increase of inflammatory cytokines in the liver. Furthermore, as expected, inflammation peaked at 24 h and subsided after 7 d. However, the knockdown of Smad7 in myeloid cells did not affect any of the investigated parameters in the CCl(4)-treated animals. In summary, our results suggest that the inhibition of TGF-β signaling via Smad7 expression in myeloid cells is dispensable for the induction and control of acute CCl(4)-induced liver injury. MDPI 2019-11-06 /pmc/articles/PMC6888233/ /pubmed/31698731 http://dx.doi.org/10.3390/ijms20225528 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Endig, Jessica
Unrau, Ludmilla
Sprezyna, Paulina
Rading, Sebasting
Karsak, Meliha
Goltz, Diane
Heukamp, Lukas C.
Tiegs, Gisa
Diehl, Linda
Acute Liver Injury after CCl(4) Administration Is Independent of Smad7 Expression in Myeloid Cells
title Acute Liver Injury after CCl(4) Administration Is Independent of Smad7 Expression in Myeloid Cells
title_full Acute Liver Injury after CCl(4) Administration Is Independent of Smad7 Expression in Myeloid Cells
title_fullStr Acute Liver Injury after CCl(4) Administration Is Independent of Smad7 Expression in Myeloid Cells
title_full_unstemmed Acute Liver Injury after CCl(4) Administration Is Independent of Smad7 Expression in Myeloid Cells
title_short Acute Liver Injury after CCl(4) Administration Is Independent of Smad7 Expression in Myeloid Cells
title_sort acute liver injury after ccl(4) administration is independent of smad7 expression in myeloid cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888233/
https://www.ncbi.nlm.nih.gov/pubmed/31698731
http://dx.doi.org/10.3390/ijms20225528
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