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1.
Nat Commun ; 15(1): 2413, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38499575

ABSTRACT

The genome's dynamic nature, exemplified by elements like extrachromosomal circular DNA (eccDNA), is crucial for biodiversity and adaptation. Yet, the role of eccDNA in plants, particularly rice, remains underexplored. Here, we identify 25,598 eccDNAs, unveiling the widespread presence of eccDNA across six rice tissues and revealing its formation as a universal and random process. Interestingly, we discover that direct repeats play a pivotal role in eccDNA formation, pointing to a unique origin mechanism. Despite eccDNA's prevalence in coding sequences, its impact on gene expression is minimal, implying its roles beyond gene regulation. We also observe the association between eccDNA's formation and minor chromosomal deletions, providing insights of its possible function in regulating genome stability. Further, we discover eccDNA specifically accumulated in rice leaves, which may be associated with DNA damage caused by environmental stressors like intense light. In summary, our research advances understanding of eccDNA's role in the genomic architecture and offers valuable insights for rice cultivation and breeding.


Subject(s)
Oryza , Oryza/genetics , DNA, Circular/genetics , Plant Breeding , DNA , Genome
2.
Nat Genet ; 55(10): 1745-1756, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37679493

ABSTRACT

Exploitation of crop heterosis is crucial for increasing global agriculture production. However, the quantitative genomic analysis of heterosis was lacking, and there is currently no effective prediction tool to optimize cross-combinations. Here 2,839 rice hybrid cultivars and 9,839 segregation individuals were resequenced and phenotyped. Our findings demonstrated that indica-indica hybrid-improving breeding was a process that broadened genetic resources, pyramided breeding-favorable alleles through combinatorial selection and collaboratively improved both parents by eliminating the inferior alleles at negative dominant loci. Furthermore, we revealed that widespread genetic complementarity contributed to indica-japonica intersubspecific heterosis in yield traits, with dominance effect loci making a greater contribution to phenotypic variance than overdominance effect loci. On the basis of the comprehensive dataset, a genomic model applicable to diverse rice varieties was developed and optimized to predict the performance of hybrid combinations. Our data offer a valuable resource for advancing the understanding and facilitating the utilization of heterosis in rice.


Subject(s)
Hybrid Vigor , Oryza , Humans , Hybrid Vigor/genetics , Oryza/genetics , Plant Breeding , Phenotype , Alleles
3.
Plant Cell ; 35(11): 4002-4019, 2023 Oct 30.
Article in English | MEDLINE | ID: mdl-37648256

ABSTRACT

Heading date (flowering time), which greatly influences regional and seasonal adaptability in rice (Oryza sativa), is regulated by many genes in different photoperiod pathways. Here, we characterized a heading date gene, Early heading date 5 (Ehd5), using a modified bulked segregant analysis method. The ehd5 mutant showed late flowering under both short-day and long-day conditions, as well as reduced yield, compared to the wild type. Ehd5, which encodes a WD40 domain-containing protein, is induced by light and follows a circadian rhythm expression pattern. Transcriptome analysis revealed that Ehd5 acts upstream of the flowering genes Early heading date 1 (Ehd1), RICE FLOWERING LOCUS T 1 (RFT1), and Heading date 3a (Hd3a). Functional analysis showed that Ehd5 directly interacts with Rice outermost cell-specific gene 4 (Roc4) and Grain number, plant height, and heading date 8 (Ghd8), which might affect the formation of Ghd7-Ghd8 complexes, resulting in increased expression of Ehd1, Hd3a, and RFT1. In a nutshell, these results demonstrate that Ehd5 functions as a positive regulator of rice flowering and provide insight into the molecular mechanisms underlying heading date.


Subject(s)
Flowers , Oryza , Circadian Rhythm , Flowers/genetics , Flowers/metabolism , Gene Expression Regulation, Plant/genetics , Oryza/genetics , Oryza/metabolism , Photoperiod , Plant Proteins/genetics , Plant Proteins/metabolism , WD40 Repeats/genetics
4.
Nat Commun ; 12(1): 2563, 2021 05 07.
Article in English | MEDLINE | ID: mdl-33963185

ABSTRACT

Non-random gene organization in eukaryotes plays a significant role in genome evolution. Here, we investigate the origin of a biosynthetic gene cluster for production of defence compounds in oat-the avenacin cluster. We elucidate the structure and organisation of this 12-gene cluster, characterise the last two missing pathway steps, and reconstitute the entire pathway in tobacco by transient expression. We show that the cluster has formed de novo since the divergence of oats in a subtelomeric region of the genome that lacks homology with other grasses, and that gene order is approximately colinear with the biosynthetic pathway. We speculate that the positioning of the late pathway genes furthest away from the telomere may mitigate against a 'self-poisoning' scenario in which toxic intermediates accumulate as a result of telomeric gene deletions. Our investigations reveal a striking example of adaptive evolution underpinned by remarkable genome plasticity.


Subject(s)
Avena/genetics , Disease Resistance/genetics , Metabolic Networks and Pathways/genetics , Telomere/genetics , Avena/metabolism , Edible Grain/genetics , Evolution, Molecular , High-Throughput Nucleotide Sequencing , In Situ Hybridization, Fluorescence , Multigene Family , RNA-Seq , Repetitive Sequences, Nucleic Acid , Saponins/biosynthesis , Saponins/chemistry , Saponins/genetics , Synteny/genetics , Nicotiana/metabolism , Whole Genome Sequencing
5.
Nat Commun ; 12(1): 2458, 2021 04 28.
Article in English | MEDLINE | ID: mdl-33911077

ABSTRACT

Miscanthus, a rhizomatous perennial plant, has great potential for bioenergy production for its high biomass and stress tolerance. We report a chromosome-scale assembly of Miscanthus lutarioriparius genome by combining Oxford Nanopore sequencing and Hi-C technologies. The 2.07-Gb assembly covers 96.64% of the genome, with contig N50 of 1.71 Mb. The centromere and telomere sequences are assembled for all 19 chromosomes and chromosome 10, respectively. Allotetraploid origin of the M. lutarioriparius is confirmed using centromeric satellite repeats. The tetraploid genome structure and several chromosomal rearrangements relative to sorghum are clearly demonstrated. Tandem duplicate genes of M. lutarioriparius are functional enriched not only in terms related to stress response, but cell wall biosynthesis. Gene families related to disease resistance, cell wall biosynthesis and metal ion transport are greatly expanded and evolved. The expansion of these families may be an important genomic basis for the enhancement of remarkable traits of M. lutarioriparius.


Subject(s)
Chromosomes, Plant/genetics , Genome, Plant/genetics , Poaceae/genetics , Base Composition/genetics , Biomass , Cell Wall/metabolism , Centromere/genetics , Chloroplasts/genetics , Computational Biology , Genetic Variation/genetics , High-Throughput Nucleotide Sequencing , Ion Transport/genetics , Photosynthesis/genetics , Phylogeny , Poaceae/classification , Sequence Analysis, DNA , Sequence Homology , Sorghum/genetics , Telomere/genetics
6.
Poult Sci ; 99(10): 4824-4831, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32988519

ABSTRACT

This study investigated the effects of dietary chitosan oligosaccharides (COS) supplementation on growth performance; corticosterone, growth hormone, and insulin-like growth factor-1 concentration; relative organ weight; liver function; meat quality; muscle glycolytic metabolism; and oxidative status in yellow-feather broilers under heat stress. A total of 108 35-day-old Chinese yellow-feather broilers (BW, 470.31 ± 13.15 g) was randomly allocated to 3 dietary treatments as follow: control group, basal diet and raised under normal temperature (24°C); HS group, basal diet and raised under cycle heat stress (34°C from 10:00 to 18:00 and 24°C for the rest time); and HSC group, basal diet with 200 mg/kg COS supplementation and raised under cycle heat stress. Each treatment had 6 replication pens and 6 broilers per pen. Results indicated that heat stress decreased ADG, ADFI, gain:feed ratio, the relative weight of thymus, bursa of Fabricius, pancreas, proventriculus, gizzard, and liver, growth hormone concentration, pH24h, muscle glycogen content, muscle superoxide dismutase and glutathione peroxidase activity, as well as increased corticosterone, alanine aminotransferase and aspartate aminotransferase level, cooking loss, muscle lactate and malondialdehyde content. Compared with the HS group, broilers in the HSC group had higher ADG, the relative weight of thymus, bursa of Fabricius, and liver, growth hormone concentration, pH24h, muscle glycogen content, muscle superoxide dismutase and glutathione peroxidase activity, and lower serum corticosterone, alanine aminotransferase and aspartate aminotransferase level, cooking loss, and muscle lactate and malondialdehyde content. In conclusion, the results suggested that COS could be used as an effective feed additive to maintain growth performance, liver function, meat quality, muscle glycolytic metabolism, and oxidative status of yellow-feather broilers under heat stress. The improved meat quality is possibly through reducing muscle glycolysis metabolism and improving muscle oxidative status by dietary COS supplementation in broilers under heat stress.


Subject(s)
Chickens , Chitosan , Dietary Supplements , Growth and Development , Heat-Shock Response , Meat , Oligosaccharides , Animal Feed/standards , Animals , Chickens/growth & development , Chickens/metabolism , Chitosan/pharmacology , Diet/veterinary , Glycolysis/drug effects , Growth and Development/drug effects , Heat-Shock Response/drug effects , Meat/standards , Muscle, Skeletal/metabolism , Oligosaccharides/pharmacology , Random Allocation
7.
Plant Biotechnol J ; 18(1): 185-194, 2020 01.
Article in English | MEDLINE | ID: mdl-31199059

ABSTRACT

Heterosis, or hybrid vigour, is a predominant phenomenon in plant genetics, serving as the basis of crop hybrid breeding, but the causative loci and genes underlying heterosis remain unclear in many crops. Here, we present a large-scale genetic analysis using 5360 offsprings from three elite maize hybrids, which identifies 628 loci underlying 19 yield-related traits with relatively high mapping resolutions. Heterotic pattern investigations of the 628 loci show that numerous loci, mostly with complete-incomplete dominance (the major one) or overdominance effects (the secondary one) for heterozygous genotypes and nearly equal proportion of advantageous alleles from both parental lines, are the major causes of strong heterosis in these hybrids. Follow-up studies for 17 heterotic loci in an independent experiment using 2225 F2 individuals suggest most heterotic effects are roughly stable between environments with a small variation. Candidate gene analysis for one major heterotic locus (ub3) in maize implies that there may exist some common genes contributing to crop heterosis. These results provide a community resource for genetics studies in maize and new implications for heterosis in plants.


Subject(s)
Genetic Loci , Hybrid Vigor , Zea mays/genetics , Alleles , Genome, Plant , Heterozygote , Phenotype
8.
Nat Commun ; 10(1): 2982, 2019 07 05.
Article in English | MEDLINE | ID: mdl-31278256

ABSTRACT

Hybrid rice breeding for exploiting hybrid vigor, heterosis, has greatly increased grain yield. However, the heterosis-related genes associated with rice grain production remain largely unknown, partly because comprehensive mapping of heterosis-related traits is still labor-intensive and time-consuming. Here, we present a quantitative trait locus (QTL) mapping method, GradedPool-Seq, for rapidly mapping QTLs by whole-genome sequencing of graded-pool samples from F2 progeny via bulked-segregant analysis. We implement this method and map-based cloning to dissect the heterotic QTL GW3p6 from the female line. We then generate the near isogenic line NIL-FH676::GW3p6 by introgressing the GW3p6 allele from the female line Guangzhan63-4S into the male inbred line Fuhui676. The NIL-FH676::GW3p6 exhibits grain yield highly increased compared to Fuhui676. This study demonstrates that it may be possible to achieve a high level of grain production in inbred rice lines without the need to construct hybrids.


Subject(s)
Chromosome Mapping/methods , Edible Grain/genetics , Hybrid Vigor/genetics , Oryza/genetics , Plant Breeding/methods , Chromosomes, Plant/genetics , Quantitative Trait Loci/genetics
9.
Plant Physiol ; 180(4): 2077-2090, 2019 08.
Article in English | MEDLINE | ID: mdl-31138620

ABSTRACT

Grain size is one of the key determinants of grain yield. Although a number of genes that control grain size in rice (Oryza sativa) have been identified, the overall regulatory networks behind this process remain poorly understood. Here, we report the map-based cloning and functional characterization of the quantitative trait locus GL6, which encodes a plant-specific plant AT-rich sequence- and zinc-binding transcription factor that regulates rice grain length and spikelet number. GL6 positively controls grain length by promoting cell proliferation in young panicles and grains. The null gl6 mutant possesses short grains, whereas overexpression of GL6 results in large grains and decreased grain number per panicle. We demonstrate that GL6 participates in RNA polymerase III transcription machinery by interacting with RNA polymerase III subunit C53 and transcription factor class C1 to regulate the expression of genes involved in rice grain development. Our findings reveal a further player involved in the regulation of rice grain size that may be exploited in future rice breeding.


Subject(s)
Edible Grain/growth & development , Edible Grain/metabolism , Oryza/growth & development , Oryza/metabolism , Transcription Factors/metabolism , Alleles , Edible Grain/genetics , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , Oryza/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/growth & development , Plants, Genetically Modified/metabolism , Quantitative Trait Loci/genetics , RNA Polymerase III/genetics , RNA Polymerase III/metabolism , Transcription Factors/genetics
10.
Sensors (Basel) ; 18(9)2018 Aug 22.
Article in English | MEDLINE | ID: mdl-30135394

ABSTRACT

Monitoring the internal force of the rocks surrounding a mine-shield tunnel for the initial support of a mine-shield tunnel, in complex geological and hydrological environments, requires bolts with specific features such as high tensile strength, low shear strength, good insulation and resistance to corrosion. As such, internal force monitoring has become an important issue in safety monitoring for such tunneling projects. In this paper, the adaptability of a mine-shield tunnel project in a corrosive environment is investigated. A fiberglass reinforced plastic (FRP) bolt with high tensile strength, low shear strength, resistance to fatigue, non-conductivity and resistance to corrosion is used as a probe in tandem with an anchor-head dynamometer to monitor the internal force of the rocks surrounding a mine-shield tunnel for initial support. Additionally, solar energy collection technology is introduced to create a remote monitoring system. Using a 2.5 km long railway tunnel located in the northeast of the Pearl River Delta of China as a case study, the present study shows that, compared with a conventional steel bolt, the FRP bolt has advantages, such as avoidance of the risks associated with the shield machine, insulation and resistance to corrosion. As a probe, the response of the FRP bolt to events such as a blasting vibration and a construction disturbance that results in internal changes in the surrounding rock demonstrates a clear pattern that is appropriate for monitoring the internal force of the rocks surrounding a mine-shield tunnel in a corrosive environment. FRP bolt-based monitoring not only provides new technological support for controlling the risk involved in the initial support of a mine-shield tunnel but can also be widely deployed in projects with special requirements for disassembly, conductivity and corrosion.

11.
Nat Genet ; 50(8): 1196, 2018 08.
Article in English | MEDLINE | ID: mdl-29858585

ABSTRACT

When published, this article did not initially appear open access. This error has been corrected, and the open access status of the paper is noted in all versions of the paper.

12.
Nat Genet ; 50(2): 278-284, 2018 02.
Article in English | MEDLINE | ID: mdl-29335547

ABSTRACT

The rich genetic diversity in Oryza sativa and Oryza rufipogon serves as the main sources in rice breeding. Large-scale resequencing has been undertaken to discover allelic variants in rice, but much of the information for genetic variation is often lost by direct mapping of short sequence reads onto the O. sativa japonica Nipponbare reference genome. Here we constructed a pan-genome dataset of the O. sativa-O. rufipogon species complex through deep sequencing and de novo assembly of 66 divergent accessions. Intergenomic comparisons identified 23 million sequence variants in the rice genome. This catalog of sequence variations includes many known quantitative trait nucleotides and will be helpful in pinpointing new causal variants that underlie complex traits. In particular, we systemically investigated the whole set of coding genes using this pan-genome data, which revealed extensive presence and absence of variation among rice accessions. This pan-genome resource will further promote evolutionary and functional studies in rice.


Subject(s)
Crops, Agricultural/genetics , Genetic Variation , Genome, Plant , Genomics/methods , Oryza/genetics , Domestication , High-Throughput Nucleotide Sequencing , Oryza/classification , Plant Breeding , Sequence Analysis, DNA
13.
Nature ; 537(7622): 629-633, 2016 09 29.
Article in English | MEDLINE | ID: mdl-27602511

ABSTRACT

Increasing grain yield is a long-term goal in crop breeding to meet the demand for global food security. Heterosis, when a hybrid shows higher performance for a trait than both parents, offers an important strategy for crop breeding. To examine the genetic basis of heterosis for yield in rice, here we generate, sequence and record the phenotypes of 10,074 F2 lines from 17 representative hybrid rice crosses. We classify modern hybrid rice varieties into three groups, representing different hybrid breeding systems. Although we do not find any heterosis-associated loci shared across all lines, within each group, a small number of genomic loci from female parents explain a large proportion of the yield advantage of hybrids over their male parents. For some of these loci, we find support for partial dominance of heterozygous locus for yield-related traits and better-parent heterosis for overall performance when all of the grain-yield traits are considered together. These results inform on the genomic architecture of heterosis and rice hybrid breeding.


Subject(s)
Genes, Plant/genetics , Genome, Plant , Hybrid Vigor/genetics , Oryza/growth & development , Oryza/genetics , Quantitative Trait Loci/genetics , Alleles , Crosses, Genetic , Genes, Dominant , Genomics , Genotype , Heterozygote , Hybridization, Genetic , Oryza/anatomy & histology , Phenotype , Plant Breeding , Sequence Analysis, DNA
14.
Nat Genet ; 48(4): 447-56, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26950093

ABSTRACT

Although genetic diversity has a cardinal role in domestication, abundant natural allelic variations across the rice genome that cause agronomically important differences between diverse varieties have not been fully explored. Here we implement an approach integrating genome-wide association testing with functional analysis on grain size in a diverse rice population. We report that a major quantitative trait locus, GLW7, encoding the plant-specific transcription factor OsSPL13, positively regulates cell size in the grain hull, resulting in enhanced rice grain length and yield. We determine that a tandem-repeat sequence in the 5' UTR of OsSPL13 alters its expression by affecting transcription and translation and that high expression of OsSPL13 is associated with large grains in tropical japonica rice. Further analysis indicates that the large-grain allele of GLW7 in tropical japonica rice was introgressed from indica varieties under artificial selection. Our study demonstrates that new genes can be effectively identified on the basis of genome-wide association data.


Subject(s)
Edible Grain/genetics , Oryza/genetics , Chromosomes, Plant/genetics , Edible Grain/anatomy & histology , Genes, Plant , Genome-Wide Association Study , Linkage Disequilibrium , Oryza/anatomy & histology , Plants, Genetically Modified , Polymorphism, Single Nucleotide , Quantitative Trait Loci , RNA, Plant/genetics , Sequence Analysis, RNA
15.
Nat Commun ; 6: 8609, 2015 Oct 19.
Article in English | MEDLINE | ID: mdl-26477832

ABSTRACT

Oilseed crops are used to produce vegetable oil. Sesame (Sesamum indicum), an oilseed crop grown worldwide, has high oil content and a small diploid genome, but the genetic basis of oil production and quality is unclear. Here we sequence 705 diverse sesame varieties to construct a haplotype map of the sesame genome and de novo assemble two representative varieties to identify sequence variations. We investigate 56 agronomic traits in four environments and identify 549 associated loci. Examination of the major loci identifies 46 candidate causative genes, including genes related to oil content, fatty acid biosynthesis and yield. Several of the candidate genes for oil content encode enzymes involved in oil metabolism. Two major genes associated with lignification and black pigmentation in the seed coat are also associated with large variation in oil content. These findings may inform breeding and improvement strategies for a broad range of oilseed crops.


Subject(s)
Genome-Wide Association Study , Sesame Oil/biosynthesis , Sesamum/genetics , Amino Acid Sequence , Genes, Plant , Molecular Sequence Data , Seeds/metabolism , Sesamum/metabolism
17.
Nat Genet ; 47(6): 625-31, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25938946

ABSTRACT

The grass carp is an important farmed fish, accounting for ∼16% of global freshwater aquaculture, and has a vegetarian diet. Here we report a 0.9-Gb draft genome of a gynogenetic female adult and a 1.07-Gb genome of a wild male adult. Genome annotation identified 27,263 protein-coding gene models in the female genome. A total of 114 scaffolds consisting of 573 Mb are anchored on 24 linkage groups. Divergence between grass carp and zebrafish is estimated to have occurred 49-54 million years ago. We identify a chromosome fusion in grass carp relative to zebrafish and report frequent crossovers between the grass carp X and Y chromosomes. We find that transcriptional activation of the mevalonate pathway and steroid biosynthesis in liver is associated with the grass carp's adaptation from a carnivorous to an herbivorous diet. We believe that the grass carp genome could serve as an initial platform for breeding better-quality fish using a genomic approach.


Subject(s)
Carps/genetics , Adaptation, Biological/genetics , Animals , Evolution, Molecular , Female , Fish Proteins/genetics , Fish Proteins/metabolism , Genome , Herbivory/genetics , Male , Molecular Sequence Annotation , Molecular Sequence Data , Sequence Analysis, DNA , Transcriptome
18.
Nat Commun ; 6: 6258, 2015 Feb 05.
Article in English | MEDLINE | ID: mdl-25651972

ABSTRACT

Exploitation of heterosis is one of the most important applications of genetics in agriculture. However, the genetic mechanisms of heterosis are only partly understood, and a global view of heterosis from a representative number of hybrid combinations is lacking. Here we develop an integrated genomic approach to construct a genome map for 1,495 elite hybrid rice varieties and their inbred parental lines. We investigate 38 agronomic traits and identify 130 associated loci. In-depth analyses of the effects of heterozygous genotypes reveal that there are only a few loci with strong overdominance effects in hybrids, but a strong correlation is observed between the yield and the number of superior alleles. While most parental inbred lines have only a small number of superior alleles, high-yielding hybrid varieties have several. We conclude that the accumulation of numerous rare superior alleles with positive dominance is an important contributor to the heterotic phenomena.


Subject(s)
Alleles , Genome, Plant , Hybrid Vigor/genetics , Hybridization, Genetic , Oryza/genetics , Agriculture , Gene-Environment Interaction , Genome-Wide Association Study , Heterozygote , Phenotype , Quantitative Trait, Heritable
19.
Planta ; 238(5): 845-57, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23907515

ABSTRACT

Characterization of tissue-specific plant gene promoters will benefit genetic improvement in crops. Here, we isolated a novel rice anther-specific plant lipid transfer protein (OsLTP6) gene through high through-put expressional profiling. The promoter of OsLTP6 was introduced to the upstream of the uidA gene, which encodes ß-glucuronidase (GUS), and transformed into rice plants for functional analysis. Histochemical and fluorometric GUS assay showed that GUS was specifically expressed in the anthers and pollens in OsLTP6 promoter::uidA transgenic plants. Transverse section of the rice anther further indicated that the OsLTP6 promoter directed the reporter gene specifically expressed in anther tapetum. To identify regulatory elements within OsLTP6 promoter region, four progressive deletions of the OsLTP6 promoter were constructed. The results indicated that the OsLTP6 promoter achieved anther-specific expression through a combination of positive and negative regulatory elements. A 26-bp motif upstream of TATA box was a key transcriptional activator for OsLTP6 gene. CAAT box and GTGA box were the putative motifs to increase the transcription level to full expression. Two negative regulatory elements were also found in two distinct regions within this promoter. They repressed the expression in leaf and stem, respectively. These results revealed the regulating complexity of anther-specific expression.


Subject(s)
Flowers/genetics , Gene Expression Regulation, Plant , Genes, Plant/genetics , Oryza/genetics , Plant Proteins/genetics , Promoter Regions, Genetic , Amino Acid Sequence , Base Sequence , Flowers/cytology , Fluorometry , Glucuronidase/metabolism , Molecular Sequence Data , Organ Specificity/genetics , Plant Proteins/chemistry , Plant Proteins/metabolism , Real-Time Polymerase Chain Reaction , Sequence Analysis, DNA , Sequence Deletion/genetics
20.
J Immunol ; 191(3): 1413-27, 2013 Aug 01.
Article in English | MEDLINE | ID: mdl-23817423

ABSTRACT

Inflammatory bowel disease (IBD) has long been a worldwide health care problem with a persistently increasing incidence. Although its clinical features have been well described, its etiology and pathogenesis remain unclear. IL-16 is a chemoattractant cytokine with various effects on cellular activities and diseases. However, the involvement of IL-16 in IBD remains poorly understood. In this study, to our knowledge we report for the first time the mechanism by which IL-16 induces intestinal inflammation by upregulating the expression of oligopeptide transporter member 1 (PepT1) in a Tetraodon nigroviridis fish model. The dextran sodium sulfate-induced colitis model in this species revealed that IL-16 levels significantly increase accompanied by elevations in PepT1 in the colon. Moreover, the signs of colitis were dramatically attenuated by IL-16 depletion using anti-IL-16 Abs. In vivo IL-16 administration induced remarkable intestinal inflammation with typical ulcerative colitis-like features, including histologic damage, inflammatory cell infiltration, increased myeloperoxidase activity, and proinflammatory cytokines expression, which corresponded with significant PepT1 upregulation in the colon. The IL-16-induced PepT1 expression and its upregulated fMLF transport were also demonstrated in vitro. To our knowledge, our study provides the first evidence of the connection between IL-16 and PepT1, which provides new insights into the molecular mechanism underlying IBD development. Additionally, this study suggests that fish species are an attractive model for studying IBD. By providing a better understanding of IL-16 biology from fish to mammals, this study should aid the development of IL-16-based therapies for IBD.


Subject(s)
Inflammation/immunology , Inflammatory Bowel Diseases/metabolism , Interleukin-16/metabolism , Intestines/immunology , Symporters/metabolism , Animals , Antibodies/immunology , Cell Line, Tumor , Dextran Sulfate , Disease Models, Animal , HeLa Cells , Humans , Inflammatory Bowel Diseases/chemically induced , Interleukin-16/immunology , Interleukin-16/pharmacology , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Peptide Transporter 1 , RNA Interference , RNA, Small Interfering , Symporters/genetics , Tetraodontiformes/metabolism , Up-Regulation
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