Universität zu Köln

Endig, Jessica, Unrau, Ludmilla, Sprezyna, Paulina, Rading, Sebasting, Karsak, Meliha, Goltz, Diane, Heukamp, Lukas C., Tiegs, Gisa and Diehl, Linda (2019). Acute Liver Injury after CCl4 Administration Is Independent of Smad7 Expression in Myeloid Cells. Int. J. Mol. Sci., 20 (22). BASEL: MDPI. ISSN 1422-0067

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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 beta (TGF-beta) 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 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-beta signaling via Smad7 expression in myeloid cells is dispensable for the induction and control of acute CCl4-induced liver injury.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Endig, Jessica UNSPECIFIED UNSPECIFIED UNSPECIFIED Unrau, Ludmilla UNSPECIFIED UNSPECIFIED UNSPECIFIED Sprezyna, Paulina UNSPECIFIED UNSPECIFIED UNSPECIFIED Rading, Sebasting UNSPECIFIED UNSPECIFIED UNSPECIFIED Karsak, Meliha UNSPECIFIED UNSPECIFIED UNSPECIFIED Goltz, Diane UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tiegs, Gisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Diehl, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-128683
DOI:	10.3390/ijms20225528
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	20
Number:	22
Date:	2019
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FIBROGENESIS; MACROPHAGES Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12868