Acute Liver Injury after CCl4 Administration Is Independent of Smad7 Expression in Myeloid Cells

Published on Nov 6, 2019in International Journal of Molecular Sciences4.556
· DOI :10.3390/IJMS20225528
Jessica Endig2
Estimated H-index: 2
(UHH: University of Hamburg),
Ludmilla Unrau3
Estimated H-index: 3
(UHH: University of Hamburg)
+ 6 AuthorsLinda Diehl23
Estimated H-index: 23
(UHH: University of Hamburg)
Sources
Abstract
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 Smad7fl/fl), we investigated the impact of Smad7 deficiency in myeloid cells on liver inflammation and regeneration using the well-established model of CCl4-mediated liver injury. Early (24/48 h) and late (7 d) time points were analyzed. We found that CCl4 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 CCl4-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 CCl4-induced liver injury.
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