Kinetics of changes in gene and microRNA expression related with muscle inflammation and protein degradation following LPS-challenge in weaned piglets.
Ontology highlight
ABSTRACT:
SUBMITTER: Kang P
PROVIDER: S-EPMC7780359 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Kinetics of changes in gene and microRNA expression related with muscle inflammation and protein degradation following LPS-challenge in weaned piglets.
Kang Ping P Huang Xingfa X Wan Zhicheng Z Liang Tianzeng T Wang Yang Y Li Xiangen X Zhang Jing J Zhu Huiling H Liu Yulan Y
Innate immunity 20201124 1
To test the dynamic changes of the expression of genes and microRNA in the gastrocnemius muscle after LPS challenge, 36 piglets were assigned to a control group (slaughtered 0 h after saline injection) and LPS groups (slaughtered at 1 h, 2 h, 4 h, 8 h, and 12 h after LPS treatment, respectively). After LPS treatment, the mRNA expression of IL-1β, IL-6, and TNF-α reached maximal levels at 1 h, 2 h, and 1 h, respectively (<i>P</i> < 0.05), and mRNA expression of TLR4, NODs, muscle-specific ring fi ...[more]
Similar Datasets
Project description:MicroRNAs (miRNAs) constitute a class of non-coding RNAs that play a crucial regulatory role in skeletal muscle development and disease. Several acute inflammation conditions including sepsis and cancer are characterized by a loss of skeletal muscle due primarily to excessive muscle catabolism. As a well-known inducer of acute inflammation, a lipopolysaccharide (LPS) challenge can cause serious skeletal muscle wasting. However, knowledge of the role of miRNAs in the course of inflammatory muscle catabolism is still very limited. In this study, RNA extracted from the skeletal muscle of pigs injected with LPS or saline was subjected to small RNA deep sequencing. We identified 304 conserved and 114 novel candidate miRNAs in the pig. Of these, four were significantly increased in the LPS-challenged samples and five were decreased. The expression of five miRNAs (ssc-miR-146a-5p, ssc-miR-221-5p, ssc-miR-148b-3p, ssc-miR-215 and ssc-miR-192) were selected for validation by quantitative polymerase chain reaction (qPCR), which found that ssc-miR-146a-5p and ssc-miR-221-5p were significantly upregulated in LPS-challenged pig skeletal muscle. Moreover, we treated mouse C2C12 myotubes with 1000 ng/mL LPS as an acute inflammation cell model. Expression of TNF-α, IL-6, muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) mRNA was strongly induced by LPS. Importantly, miR-146a-5p and miR-221-5p also showed markedly increased expression in LPS-treated C2C12 myotubes, suggesting the two miRNAs may be involved in muscle catabolism systems in response to acute inflammation caused by a LPS challenge. To our knowledge, this study is the first to examine miRNA expression profiles in weaned pig skeletal muscle challenged with LPS, and furthers our understanding of miRNA function in the regulation of inflammatory muscle catabolism.
| S-EPMC4613317 | biostudies-literature
Project description:UnlabelledBackgroundShifts in intracellular arginine (Arg) and sulfur amino acid (SAA) redox metabolism modulate macrophage activation, polarization and phenotype. Despite their importance in inflammation and redox regulatory pathways, comprehensive analysis of these metabolic networks was not previously possible with existing analytical methods.MethodsThe Arg/thiol redox LC-MS/MS metabolomics assay permits simultaneous assessment of amino acids and derivative products generated from Arg and SAA metabolism. Using this assay, LPS-induced changes in macrophage amino acid metabolism were monitored to identify pathway shifts during activation and their linkage to cellular redox regulation.ResultsMetabolite concentrations most significantly changed after treatment of a macrophage-like cell line (RAW) with LPS for 24 hrs were citrulline (Cit) (48-fold increase), ornithine (Orn) (8.5-fold increase), arginine (Arg) (66% decrease), and aspartic acid (Asp) (73% decrease). The ratio Cit + Orn/Arg + Asp (CO/AA) was more sensitive to LPS stimulation than other amino acid ratios commonly used to measure LPS-dependent inflammation (e.g., SAM/SAH, GSH/GSSG) and total media NOx. The CO/AA ratio was also the first ratio to change significantly after LPS treatment (4 hrs). Changes in the overall metabolomic profile over time indicated that metabolic pathways shifted from Arg catabolism to thiol oxidation.ConclusionsSimultaneous quantification of Arg and SAA metabolic pathway shifts following LPS challenge of macrophage indicate that, in this system, the Arg-Citrulline/NO cycle and arginase pathways are the amino acid metabolic pathways most sensitive to LPS-challenge. The cellular (Cit + Orn)/(Arg + Asp) ratio, which summarizes this pathway, was more responsive to lower concentrations of LPS and responded earlier than other metabolic biomarkers of macrophage activation including GSH redox. It is suggested that the CO/AA ratio is a redox- independent early biomarker of macrophage activation. The ability to measure both the CO/AA and GSH-redox ratios simultaneously permits quantification of the relative effects of LPS challenge on macrophage inflammation and oxidative stress pathways. The use of this assay in humans is discussed, as are clinical implications.
| S-EPMC3507808 | biostudies-literature
Project description:Transcriptional profiling of 25d old piglets comparing control untreated suckling jejunum with weaned piglets' jejunum. The goal was to gain new insight into the interaction between weaning and intestinal function.A keen interest is paid in deciphering expression changes of apoptosis or cell cycle control genes. The statistical analysis of gene ontology revealed that most of these altered genes are metabolic-related enzymes and regulators which may involved in the biological regulation, developmental process, and cellular process. Weaning also causes alterations in various immune response pathways. Results likely indicate that weaning induced cell cycle arrest, enhanced apoptosis, and inhibited cell proliferation.
2014-05-01 | GSE48050 | GEO
Project description:Transcriptional profiling of 25d old piglets comparing control untreated suckling jejunum with weaned piglets' jejunum. The goal was to gain new insight into the interaction between weaning and intestinal function.A keen interest is paid in deciphering expression changes of apoptosis or cell cycle control genes. The statistical analysis of gene ontology revealed that most of these altered genes are metabolic-related enzymes and regulators which may involved in the biological regulation, developmental process, and cellular process. Weaning also causes alterations in various immune response pathways. Results likely indicate that weaning induced cell cycle arrest, enhanced apoptosis, and inhibited cell proliferation. Two-condition experiment, suckling control piglets' jejunum vs. weaned piglets' jejunum. Biological replicates: 4 control replicates, 4 weaned replicates.
2014-05-01 | E-GEOD-48050 | biostudies-arrayexpress
Project description:Here we investigated the influence of LPS-induced gut injury on antioxidant homeostasis, mitochondrial (mt) function and the level of mitophagy in piglets. The results showed that LPS-induced intestinal injury decreased the transepithelial electrical resistance, increased the paracellular permeability of F1TC dextran 4?kDa, and decreased the expression of claudin-1, occludin and zonula occludens-1 in the jejunum compared with the control group. LPS decreased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and increased the content of malondialdehyde in the jejunum. Meanwhile, the expression of SOD-related genes ( Cu/Zn-SOD, Mn-SOD) and GSH-Px-related genes ( GPX-1, GPX-4) declined in LPS-challenged pigs compared with the control. LPS also increased TNF-?, IL-6, IL-8 and IL-1? mRNA expression. LPS induced mt dysfunction, as demonstrated by increased reactive oxygen species production and decreased membrane potential of intestinal mitochondria, intestinal content of mt DNA and activities of the intestinal mt respiratory chain. Furthermore, LPS induced an increase in expression of mitophagy related proteins, PTEN-induced putative kinase (PINK1) and Parkin in the intestinal mitochondria, as well as an enhancement of the ratio of light chain 3-II (LC3-II) to LC3-I content in the jejunal mucosa. These results suggested that LPS-induced intestinal injury accompanied by disrupted antioxidant homeostasis, caused mt dysfunction and triggered mitophagy.
| S-EPMC6830921 | biostudies-literature
Project description:This study was conducted to evaluate the effect of dietary supplementation with Lactobacillus delbrueckii (LAB) on intestinal morphology, barrier function, immune response, and antioxidant capacity in weaned piglets challenged with lipopolysaccharide (LPS). A total of 36 two-line crossbred (Landrace?×?large Yorkshire) weaned piglets (28 days old) were divided into three groups: (1) nonchallenged control (CON); (2) LPS-challenged control (LPS); and (3) LAB+LPS treatment (0.2% LAB+LPS). Compared to the LPS piglets, the LAB+LPS piglets improved intestinal morphology, indicated by greater (P < 0.05) villus height in the duodenum and ileum; villus height?:?crypt depth ratio in the duodenum, jejunum, and ileum, as well as decreased (P < 0.05) crypt depth in the jejunum and ileum; and better intestinal barrier function, indicated by upregulated (P < 0.05) mRNA expression of tight junction proteins in the intestinal mucosa. Moreover, compared to the LPS piglets, LAB significantly decreased (P < 0.05) concentrations of TNF-? and IL-1? in the small intestine and increased (P < 0.05) IL-10 levels in the jejunum and ileum. Additionally, LAB increased (P < 0.05) T-AOC activities of the colon, GSH concentrations of the jejunum, and mRNA expression of CAT and Cu/Zn-SOD, while reduced (P < 0.05) MDA concentrations in the jejunum and ileum in LPS-changed piglets. Collectively, our results indicate that supplementation of LAB improved intestinal integrity and immune response and alleviated intestinal oxidative damage in LPS-challenged piglets.
| S-EPMC7035547 | biostudies-literature
Project description:Development of immune competence in pigs is important for resilience, disease resistance, and performance later in life. Dietary interventions in early life can contribute to immune system development. Use of model dietary interventions, such as diets with a high concentration of zinc, can contribute to the understanding of the interactions between the diet, the intestinal microbiota and intestinal tissues. The aim of the present study was to evaluate the effects of provision of a diet with a high concentration of zinc (Zn, 2690 mg/kg), as model intervention, as compared to provision of a control diet with a regular Zn concentration (100 mg/kg) during a period of nine days during the post weaning period (d 14-23 post weaning (pw)), on the composition of the intestinal microbiota and gene expression in the intestinal mucosa on d 23 and 35 pw (12 d after the termination of the Zn intervention). Whole genome gene expression analysis of the jejunal and ileal mucosa revealed a small overall time-treatment interaction effect at d 23 pw in both intestinal tissues. In both jejunal and ileal mucosa various genes/probes were differentially up or down regulated between treatments. In intestinal tissue samples obtained on d 35 no differences in gene expression were observed. Probes of d 23 pw that were differently expressed and had an annotation were subsequently used as input for further functional analysis using DAVID and Gene Decks databases. The analysis did not result in the identification of gene sets that were differentially expressed between dietary treatments. However, it was shown that a number of upregulated genes in the jejunal mucosa on d 23 pw by the high zinc intervention are involved in pathways related to mineral absorption, immune signalling and cell energy metabolism (glycolysis and gluconeogenesis). A few down regulated genes by the Zn intervention are also involved in immune signalling pathways. It was concluded from the present study that provision of a diet with a high concentration of zinc as zinc oxide during a short period of time (9 days) to piglets in the post weaning period (d 14-23 pw) induces differences on the intestinal expression of genes in part related to the functioning of the local innate immune system. The high dietary zinc intervention can therefore be considered as a suitable model for studying relationships between dietary interventions and development of immune competence in post weaning piglets.
2017-04-19 | GSE94370 | GEO
Project description:Melatonin has been reported to play crucial roles in regulating meat quality, improving reproductive properties and maintaining intestinal health in animal production, but whether it regulates skeletal muscle development in weaned piglet is rarely studied. This study was conducted to investigate the effects of melatonin on growth performance, skeletal muscle development and lipid metabolism in animals by intragastric administration of melatonin solution. Twelve 28-day-old DLY (Duroc × Landrace × Yorkshire) weaned piglets with similar body weight were randomly divided into two groups: control group and melatonin group. The results showed that melatonin supplementation for 23 days had no effect on growth performance, but significantly reduced serum glucose content (P<0.05). Remarkably, melatonin increased longissimus dorsi muscle (LDM) weight, eye muscle area and decreased the liver weight in weaned piglets (P<0.05). In addition, the cross-sectional area of muscle fibers was increased (P<0.05), while triglyceride (TG) levels were decreased in LDM and psoas major muscle (PMM) by melatonin treatment (P<0.05). Transcriptome sequencing showed melatonin induced the expression of genes related to skeletal muscle hypertrophy and fatty acid oxidation. Enrichment analysis indicated that melatonin regulated cholesterol metabolism, protein digestion and absorption and mitophagy signaling pathways in muscle. Gene set enrichment analysis (GSEA) also confirmed the effects of melatonin on skeletal muscle development and mitochondrial structure and function. Moreover, quantitative real-time polymerase chain reaction (qPCR) analysis revealed that melatonin supplementation elevated the gene expression of cell differentiation and muscle fiber development, including paired box 7 (PAX7), myogenin (MYOG), myosin heavy chain (MYHC) ⅡA and MYHC ⅡB (P<0.05), which was accompanied by increased insulin like growth factor 1 (IGF1) and insulin like growth factor binding protein 5 (IGFBP5) expression in LDM (P<0.05). Additionally, melatonin regulated lipid metabolism and activated mitochondrial function in muscle by increasing the mRNA abundance of cytochrome c oxidase subunit 6A (COX6A), COX5B and carnitine palmitoyltransferase 2 (CPT2) and decreasing the mRNA expression of peroxisome proliferator activated receptor gamma (PPARG), Acetyl-CoA carboxylase (ACC) and fatty acid binding protein 4 (FABP4) (P<0.05). Together, our results suggest that melatonin could promote skeletal muscle growth and muscle fiber hypertrophy, improve mitochondrial function and decrease fat deposition in muscle.
2023-10-02 | GSE237322 | GEO
Project description:Weaning stress induces tissue injuries and impairs health and growth in piglets, especially during the first week post-weaning. MicroRNAs (miRNAs) play vital roles in regulating stresses and diseases. Our previous study found multiple differentially expressed miRNAs in small intestine of piglets at four days post-weaning. To better understand the roles of miRNAs during weaning stress, we analyzed the serum miRNA expressional profile in weaned piglets (at four days post-weaning) and in suckling piglets (control) of the same age using miRNA microarray technology. We detected a total of 300 expressed miRNAs, 179 miRNAs of which were differentially expressed between the two groups. The miRNA microarray results were validated by RT-qPCR. The biological functions of these differentially expressed miRNAs were predicted by GO terms and KEGG pathway annotations. We identified 10 highly expressed miRNAs in weaned piglets including miR-31, miR-205, and miR-21 (upregulated) and miR-144, miR-30c-5p, miR-363, miR-194a, miR-186, miR-150, and miR-194b-5p (downregulated). Additionally, miR-194b-5p expression was significantly downregulated in serum and small intestine of weaned piglets. Our results suggest that weaning stress affects serum miRNA profiles in piglets. And serum miR-194b-5p levels can reflect its expressional changes in small intestine of piglets by weaning stress.
| S-EPMC5025173 | biostudies-literature
Project description:Human infants or piglets are vulnerable to intestinal microbe-caused disorders and inflammation due to their rapidly changing gut microbiota and immaturity of their immune systems at weaning. Resveratrol and curcumin have significant anti-inflammatory, bacteria-regulating and immune-promoting effects. The purpose of this study was to investigate whether dietary supplementation with resveratrol and curcumin can change the intestinal microbiota and alleviate intestinal inflammation induced by weaning in piglets. One hundred eighty piglets weaned at 21 ± 2 d were fed a control diet (CON group) or supplemented diet (300 mg/kg of antibiotics, ANT group; 300 mg/kg of resveratrol and curcumin, respectively, HRC group; 100 mg/kg of resveratrol and curcumin, respectively, LRC group; 300 mg/kg of resveratrol, RES group; 300 mg/kg of curcumin, CUR group) for 28 days. The results showed that compared with the CON group, curcumin alone and antibiotics decreased the copy numbers of Escherichia coli. Both curcumin and resveratrol down-regulated the level of Toll-like-receptor 4 mRNA and protein expression in the intestine to inhibit the release of critical inflammation molecules (interleukin-1β, tumor necrosis factor-α), and increase the secretion of immunoglobulin. Our results suggested that curcumin and resveratrol can regulate weaned piglet gut microbiota, down-regulate the TLR4 signaling pathway, alleviate intestinal inflammation, and ultimately increase intestinal immune function.
| S-EPMC6479679 | biostudies-literature