Acute Liver Injury after CCl4 Administration is Independent of Smad7 Expression in Myeloid Cells
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Acute Liver Injury after CCl4 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.
In: INT J MOL SCI, Vol. 20, No. 22, 06.11.2019.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Acute Liver Injury after CCl4 Administration is Independent of Smad7 Expression in Myeloid Cells
AU - Endig, Jessica
AU - Unrau, Ludmilla
AU - Sprezyna, Paulina
AU - Rading, Sebasting
AU - Karsak, Meliha
AU - Goltz, Diane
AU - Heukamp, Lukas C
AU - Tiegs, Gisa
AU - Diehl, Linda
PY - 2019/11/6
Y1 - 2019/11/6
N2 - 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.
AB - 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.
U2 - 10.3390/ijms20225528
DO - 10.3390/ijms20225528
M3 - SCORING: Journal article
C2 - 31698731
VL - 20
JO - INT J MOL SCI
JF - INT J MOL SCI
SN - 1661-6596
IS - 22
ER -
