Humanized xenobiotic response in mice expressing nuclear receptor SXR

Wen Xie; Joyce L. Barwick; Michael Downes; Bruce Blumberg; Cynthia M. Simon; Michael C. Nelson; Brent A. Neuschwander-Tetri; Elizabeth M. Brunt; Philip S. Guzelian; Ronald M. Evans

doi:10.1038/35019116

Humanized xenobiotic response in mice expressing nuclear receptor SXR

Nature ◽

10.1038/35019116 ◽

2000 ◽

Vol 406 (6794) ◽

pp. 435-439 ◽

Cited By ~ 488

Author(s):

Wen Xie ◽

Joyce L. Barwick ◽

Michael Downes ◽

Bruce Blumberg ◽

Cynthia M. Simon ◽

...

Keyword(s):

Nuclear Receptor ◽

Xenobiotic Response

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The Nuclear Receptor Seven Up Regulates Genes Involved in Immunity and Xenobiotic Response in the Adult Drosophila Female Fat Body

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401745 ◽

2020 ◽

Vol 10 (12) ◽

pp. 4625-4635

Author(s):

Lesley N. Weaver ◽

Daniela Drummond-Barbosa

Keyword(s):

Nuclear Receptors ◽

Nuclear Receptor ◽

Adult Female ◽

Fat Body ◽

Peripheral Tissues ◽

Immune Genes ◽

Xenobiotic Detoxification ◽

Intrinsic Roles ◽

Xenobiotic Response ◽

Adult Drosophila

The physiology of organisms depends on inter-organ communication in response to changes in the environment. Nuclear receptors are broadly expressed transcription factors that respond to circulating molecules to control many biological processes, including immunity, detoxification, and reproduction. Although the tissue-intrinsic roles of nuclear receptors in reproduction have been extensively studied, there is increasing evidence that nuclear receptor signaling in peripheral tissues can also influence oogenesis. We previously showed that the Drosophila nuclear receptor Seven up (Svp) is required in the adult fat body to regulate distinct steps of oogenesis; however, the relevant downstream targets of Svp remain unknown. Here, we took an RNA sequencing approach to identify candidate Svp targets specifically in the adult female fat body that might mediate this response. svp knockdown in the adult female fat body significantly downregulated immune genes involved in the first line of pathogen defense, suggesting a role for Svp in stimulating early immunity. In addition, we found that Svp transcriptionally regulates genes involved in each step of the xenobiotic detoxification response. Based on these findings, we propose a testable model in which Svp functions in the adult female fat body to stimulate early defense against pathogens and facilitate detoxification as part of its mechanisms to promote oogenesis.

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