Dataset Information

Disruption of Trim9 function abrogates macrophage motility in vivo.

ABSTRACT: The vertebrate immune response comprises multiple molecular and cellular components that interface to provide defense against pathogens. Because of the dynamic complexity of the immune system and its interdependent innate and adaptive functionality, an understanding of the whole-organism response to pathogen exposure remains unresolved. Zebrafish larvae provide a unique model for overcoming this obstacle, because larvae are protected against pathogens while lacking a functional adaptive immune system during the first few weeks of life. Zebrafish larvae were exposed to immune agonists for various lengths of time, and a microarray transcriptome analysis was executed. This strategy identified known immune response genes, as well as genes with unknown immune function, including the E3 ubiquitin ligase tripartite motif-9 (Trim9). Although trim9 expression was originally described as "brain specific," its expression has been reported in stimulated human M?s. In this study, we found elevated levels of trim9 transcripts in vivo in zebrafish M?s after immune stimulation. Trim9 has been implicated in axonal migration, and we therefore investigated the impact of Trim9 disruption on M? motility and found that M? chemotaxis and cellular architecture are subsequently impaired in vivo. These results demonstrate that Trim9 mediates cellular movement and migration in M?s as well as neurons.

SUBMITTER: Tokarz DA

PROVIDER: S-EPMC6608060 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Disruption of Trim9 function abrogates macrophage motility in vivo.

Tokarz Debra A DA Heffelfinger Amy K AK Jima Dereje D DD Gerlach Jamie J Shah Radhika N RN Rodriguez-Nunez Ivan I Kortum Amanda N AN Fletcher Ashley A AA Nordone Shila K SK Law J McHugh JM Heber Steffen S Yoder Jeffrey A JA

Journal of leukocyte biology 20171011 6

The vertebrate immune response comprises multiple molecular and cellular components that interface to provide defense against pathogens. Because of the dynamic complexity of the immune system and its interdependent innate and adaptive functionality, an understanding of the whole-organism response to pathogen exposure remains unresolved. Zebrafish larvae provide a unique model for overcoming this obstacle, because larvae are protected against pathogens while lacking a functional adaptive immune s ...[more]

PMID: 29021367

Similar Datasets

Project description:IntroductionHepatocellular carcinoma (HCC) is the most common type of primary liver cancers. It is an aggressive neoplasm with dismal outcome because most of the patients present with an advanced-stage disease, which precludes curative surgical options. Therefore, these patients require systemic therapies that typically induce small improvements in overall survival. Hence, it is crucial to identify new and promising therapeutic targets for HCC to improve the current outcome. The liver is a key organ in the signaling cascade triggered by the growth hormone receptor (GHR). Previous studies have shown that GHR signaling stimulates the proliferation and regeneration of liver cells and tissues; however, a definitive role of GHR signaling in HCC pathogenesis has not been identified.MethodsIn this study, we used a direct and specific approach to analyze the role of GHR in HCC development. This approach encompasses mice with global (Ghr-/- ) or liver-specific (LiGhr-/- ) disruption of GHR expression, and the injection of diethylnitrosamine (DEN) to develop HCC in these mice.ResultsOur data show that DEN induced HCC in a substantial majority of the Ghr+/+ (93.5%) and Ghr +/- (87.1%) mice but not in the Ghr-/- (5.6%) mice (P < 0.0001). Although 57.7% of LiGhr-/- mice developed HCC after injection of DEN, these mice had significantly fewer tumors than LiGhr+/+ (P < 0.001), which implies that the expression of GHR in the liver cells might increase tumor burden. Notably, the pathologic, histologic, and biochemical characteristics of DEN-induced HCC in mice resembled to a great extent human HCC, despite the fact that etiologically this model does not mimic this cancer in humans. Our data also show that the effects of DEN on mice livers were primarily related to its carcinogenic effects and ability to induce HCC, with minimal effects related to toxic effects.ConclusionCollectively, our data support an important role of GHR in HCC development, and suggest that exploiting GHR signaling may represent a promising approach to treat HCC.

Dataset Information

Disruption of Trim9 function abrogates macrophage motility in vivo.

Publications

Disruption of Trim9 function abrogates macrophage motility in vivo.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets