Antibacterial and Antiviral Roles of a Fish β-Defensin Expressed Both in Pituitary and Testis

Jin, Junyan; Zhou, Li; Wang, Yang; Li, Zhi; Zhao, Jianmin; Zhang, Qi-Ya; Gui, Jian‐Fang

doi:10.1371/journal.pone.0012883

Cited by 96 publications

(68 citation statements)

References 70 publications

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“…BD-1 is generally expressed in epithelial cells of the gastrointestinal and broncho-respiratory tract, tissues involved in host defense, and only one study so far has reported BD-1 expression in the posterior lobe of the pituitary (neurohypophysis) of the fish orange-spotted grouper, where it plays a still unidentified role (46).…”

Section: Discussionmentioning

confidence: 99%

Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas

Lee

Wiedemann

Groß

et al. 2015

Clinical Cancer Research

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Purpose: Novel therapeutic approaches are needed to improve the postoperative management of residual nonfunctioning pituitary adenomas (NFPA), given their high relapse rate. Here, we evaluated the antitumor efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in the only available model of spontaneous NFPAs (MENX rats).Experimental Design: Organotypic cultures of rat primary NFPAs were incubated with NVP-BEZ235 and assessed for cell viability, proliferation, apoptosis, and PI3K/mTOR inhibition. NVP-BEZ235, or placebo, was administered to MENX rats and tumor response was monitored noninvasively by diffusion weighted-magnetic resonance imaging (DW-MRI). Following treatment, tumor tissues were investigated for cell proliferation, apoptosis, and PI3K/mTOR inhibition. Genes mediating the cytotoxic activity of NVP-BEZ235 were identified by gene-expression profiling. Among them, Defb1, encoding beta-defensin 1, was further studied for its role in pituitary cells and in human pancreatic neuroendocrine tumor (NET) cells.Results: NVP-BEZ235 showed antiproliferative and pro-cell death activities against NFPAs both in vitro and in vivo, and the response to the drug correlated with inhibition of the PI3K pathway. DW-MRI identified early functional changes (decreased cellularity) in the adenomas before their size was affected and emerged as a useful modality to assess therapy response. The cytotoxic effect of PI3K/mTOR blockade in NFPA was mediated by several genes, including Defb1. NVP-BEZ235 treatment induced Defb1 expression in NFPAs in vitro and in vivo, and in pancreatic NET cells. High Defb1 levels sensitized NET cells to PI3K/mTOR inhibition.Conclusions: Our findings provide rationale for clinical investigation of PI3K/mTOR inhibition in NFPAs and identify novel effectors of PI3K-mediated neuroendocrine cell survival.

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Section: Discussionmentioning

confidence: 99%

Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas

Lee

Wiedemann

Groß

et al. 2015

Clinical Cancer Research

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“…Thus, the remaining pAbs were trout CAMP specific. Western blot was performed to analyze the reactivity of the pAbs with trout CAMPs as previously described (25).…”

Section: Peptide Synthesismentioning

confidence: 99%

Distinctive Structural Hallmarks and Biological Activities of the Multiple Cathelicidin Antimicrobial Peptides in a Primitive Teleost Fish

Zhang

et al. 2015

The Journal of Immunology

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Cathelicidin antimicrobial peptides (CAMPs) represent a crucial component of the innate immune system in vertebrates. Although widely studied in mammals, little is known about the structure and function of fish CAMPs. Further to the previous findings, two more cathelicidin genes and multiple transcripts from rainbow trout were identified in the present study. Interestingly, we found that trout have evolved energy-saving forms of cathelicidins with the total deletion of the characteristic cathelin-like domain. Sequence analysis revealed that salmonid CAMPs have formed a special class of antimicrobial peptides in vertebrates with three distinctive hallmarks: the N terminus is intensified by positive charges, the central region consists of repetitive motifs based on RPGGGS, and the C terminus is lowly charged. Immunofluorescence localization of trout CAMPs demonstrated that these peptides expressed mainly at the mucosal layer of gut. Meanwhile, signals around sinusoids were also detected in head kidney. Moreover, the biological activities of trout CAMPs were proved to be mediated by the N terminus. Additionally, the repetitive motifs characteristically existing in Salmonidae increased the structural flexibilities of peptides and further increased the antibacterial and IL-8–stimulating activities. Unlike most α helical and cytotoxic mammalian CAMPs, trout CAMPs, mainly consisting of β-sheet and random coil, exhibited no cytotoxic activities. The distinctive structural features of trout CAMPs provide new insights into the understanding of the evolution of CAMPs in vertebrates. Moreover, the high bacterial membrane selectivity of trout CAMPs will help to design excellent peptide antibiotics.

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“…Significantly, some novel interferon-inducible genes have been found [121], and their functional roles and signaling pathways have been well understood in fish [122][123][124]. Additionally, several candidate genes, such as PKR [125], PKR-like (or called PKZ) [126], β-Defensin [127], TRBP [128], C-type lectin [129], Enzyme E2 [130], MDA5 and LGP2 [131], have been revealed to play crucial roles in the antiviral defense response of fish and shrimp.…”

Section: Disease Resistance Trait and Candidate Disease Resistance-rementioning

confidence: 99%

Molecular basis and genetic improvement of economically important traits in aquaculture animals

2012

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Aquaculture has been believed to be a major Chinese contribution to the world. In recent 20 years, genome and other genetic technologies have promoted significant advances in basic studies on molecular basis and genetic improvement of aquaculture animals, and complete genomes of some main aquaculture animals have been sequenced or announced to be sequenced since the beginning of this century. Here, we review some significant breakthrough progress of aquaculture genetic improvement technologies including genome technologies, somatic cell nuclear transfer and stem cell technologies, outline the molecular basis of several economically important traits including reproduction, sex, growth, disease resistance, cold tolerance and hypoxia tolerance, and present a series of candidate trait-related genes. Finally, some application cases of genetic improvement are introduced in aquaculture animals, especially in China, and several development trends are highlighted in the near future.

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Antibacterial and Antiviral Roles of a Fish β-Defensin Expressed Both in Pituitary and Testis

Cited by 96 publications

References 70 publications

Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas

Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas

Distinctive Structural Hallmarks and Biological Activities of the Multiple Cathelicidin Antimicrobial Peptides in a Primitive Teleost Fish

Molecular basis and genetic improvement of economically important traits in aquaculture animals

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