IGF-1R Expression Research Articles

The Role of Insulin-like Growth Factor-Axis and Mitotic Index in South Indian Neonates with Small for Gestational Age

Objective IGF-axis and mitotic capacity of cells play a vital role in fetal growth. We compared IGF1, IGF2, and IGFBP3 protein levels, mitotic indices, IGFR1 and IGFR2 mRNA expression in appropriate for gestational age (AGA) and small for gestational age (SGA) neonates of Indian women. Methods Cord blood (n = 80) and placental samples (n = 40) were collected from AGA and SGA neonates. Plasma IGF1, IGF2, and IGFBP3 proteins were measured by ELISA. IGFR1 and IGFR2 mRNA expression in the placenta were analyzed by qRT-PCR. Cord blood was cultured in vitro and mitotic index was obtained. Results IGF1 (p = 1), and IGF2 (p = 0.69) protein levels did not differ, whereas IGFBP3 (p = 0.02) was significantly less in SGA compared to AGA neonates. Down-regulation of IGFR1 (3.9-folds) and IGFR2 (2.8-folds) mRNA and reduced mitotic index of lymphocytes was observed in SGA (p = 0.001) compared to AGA neonates. Conclusion Our results showed that, SGA neonates displayed down-regulated IGFR1 and IGFR2 mRNA, decreased IGFBP3 protein and mitotic index.

Supplementation with Fermented Feedstuff Enhances Orexin Expression and Secretion Associated with Increased Feed Intake and Weight Gain in Weaned Pigs.

Simple SummaryIn weaned pigs, finding a strategy to improve the health status while also enhancing the growth performance of piglets under weaning stress through nutritional measures is an important issue that needs to be solved. Supplementation with fermented feedstuff improves the feed intake and growth performance of weaned pigs, but the exact mechanism behind this remains unclear. Hence, the present study evaluated the effects of fermented feedstuff on the performance and gastrointestinal hormones involved in feed intake and growth in weaned pigs. The results of our study showed that dietary supplementation with fermented feedstuff improved the growth performance of weaned pigs by increasing orexin, IGF-1, and IGFR levels.The health status of weaned pigs is crucial for their subsequent growth performance. Supplementation with fermented feedstuff is able to improve the feed intake and growth of weaned pigs; however, the exact mechanism behind this is not clear. Hence, in the present study a total of 320 Duroc × Landrace × Yorkshire weaned pigs were selected and allocated to the following two groups: unfermented diet group (UFD) and fermented diet group (FD). The experimental period lasted 21 days. At the end of the experiment, feces, blood, and gastrointestinal tissue samples (including the stomach, jejunum, and ileum) were collected and used for further analysis. The results of growth performance suggested that the FD group had significantly increased (p < 0.05) average daily feed intake (ADFI) and average daily gain (ADG) during the first week, during the last two weeks, and over the entire three-week period compared with the UFD group. The results of the apparent nutrient digestibility of pigs showed that, compared with the UFD group, the FD group showed increased phosphorus (p < 0.05) and CP (p < 0.1) digestibility. There were no significant differences in the serum biochemical parameters between the UFD and FD groups. Moreover, our results showed that the FD group showed significantly increased gene expression of SGLT1 and PepT1 in the jejunum (p < 0.05). Compared with the UFD group, the FD group showed an increased (p < 0.05) serum orexin level and prepro-orexin (PPOX) expression in the gastric fundus, jejunum, and ileum mucosa and increased IGF-1 and IGFR expression in the jejunum. Collectively, these results indicated that supplementation with fermented feedstuff in the diet effectively enhanced the feed intake and growth of weaned pigs and that this may have been caused by the increased orexin, IGF-1, and IGFR serum levels.

Molecular cloning, characterization, and tissue distribution of c-Myc from blood clam Tegillarca granosa and its role in cadmium-induced stress response

Cadmium (Cd) pollution threatens the cultivation of the blood clam Tegillarca granosa (T. granosa) in coastal regions of the East China Sea. The molecular mechanisms regulating Cd stress response and detoxification in blood clams are largely unclear. In the present study, the full-length T. granosa c-Myc (Tgc-Myc) cDNA was cloned for the first time. The 3063-bp cDNA consisted of a 129-bp 5′ untranslated region (UTR), a 1746-bp 3′ UTR, and a 1188-bp open reading frame encoding a predicted protein of 395 amino acid residues. The predicted protein had a calculated molecular weight of 44.9 kDa and an estimated isoelectric point of 6.82. The predicted protein contained an N-terminal transactivation domain and a C-terminal basic helix-loop-helix leucine zipper domain, which are conserved functional domains of c-Myc proteins. Tgc-Myc showed broad tissue distribution in blood clams, with the highest expression detected in the gill and hepatopancreas. Exposure to Cd, a major heavy metal pollutant in coastal regions of the East China Sea, induced Tgc-Myc expression in gill tissues. Tgc-Myc knockdown led to reduced expression of a variety of stress response/detoxification genes in blood clams cultivated in Cd-contaminated seawater. Tgc-Myc knockdown also led to decreased expression of IGF1R, a proto-oncogene that promotes cell proliferation. These findings indicated that Tgc-Myc regulates Cd-induced stress response and detoxification in blood clams. The upregulation of Tgc-Myc may serve as an approach to generate strains with an enhanced detoxification response and consequently a low heavy metal buildup.

Effects of starter feeding and early weaning on developmental expressions of IGF-I gene in liver and IGF-IR gene in rumen of lambs from birth to eighty-four days of age

The early weaning and starter feeding have significant effects on lamb growth and digestive tract development. However, it is not clear whether the expression of IGF-1/IGF-1R genes could be affected by feeding starter and weaning. Therefore, a total of 102 Hu male neonatal lambs were randomly divided into 3 groups: fed with starter at 42d + weaned at 56d (group A), fed with starter at 7d + weaned at 28d (group B) and fed with starter at 7d + weaned at 56d (group C), to explore the effects of starter feeding and weaning age on developmental expressions of IGF-I gene in liver and IGF-IR gene in rumen of Hu sheep. The results showed that IGF-I and IGF-IR genes were expressed extensively in various tissues of lambs, the expression of IGF-I was significantly higher in liver (p < 0.01), while the expression of IGF-IR was higher in rumen among gastrointestinal tissues. The mRNA level of IGF-I of group C was strikingly higher than that of group A at 28, 70, and 84d (p < 0.01) in liver, respectively. Rumen mRNA level of IGF-IR of group C was prominently higher than that of group A at 70d and 84d (p < 0.05), respectively. However, IGF-IR expression of group A was higher than that of group C at 14 and 42d (p < 0.05). The mRNA level of IGF-I of group B was significantly higher than that of group C at 42, 56, 70, and 84d (p < 0.01) in liver, while IGF-IR expression of group B was higher than that of group C at 70d (p < 0.01). In conclusion, early weaning and starter feeding affected liver IGF-I mRNA and rumen IGF-IR mRNA expression.

Expression of IGFS and IGF1R in the pregnant uterus and placenta of dogs

Expression of IGFS and IGF1R in the pregnant uterus and placenta of dogs

Effects of heroin self-administration and forced withdrawal on the expression of genes related to the mTOR network in the basolateral complex of the amygdala of male Lewis rats

RationaleThe development of substance use disorders involves long-lasting adaptations in specific brain areas that result in an elevated risk of relapse. Some of these adaptations are regulated by the mTOR network, a signalling system that integrates extracellular and intracellular stimuli and modulates several processes related to plasticity. While the role of the mTOR network in cocaine- and alcohol-related disorders is well established, little is known about its participation in opiate use disorders.ObjectivesTo use a heroin self-administration and a withdrawal protocol that induce incubation of heroin-seeking in male rats and study the associated effects on the expression of several genes related to the mTOR system and, in the specific case of Rictor, its respective translated protein and phosphorylation.ResultsWe found that heroin self-administration elicited an increase in the expression of the genes Igf1r, Igf2r, Akt2 and Gsk3a in the basolateral complex of the amygdala, which was not as evident at 30 days of withdrawal. We also found an increase in the expression of Rictor (a protein of the mTOR complex 2) after heroin self-administration compared to the saline group, which was occluded at the 30-day withdrawal period. The activation levels of Rictor, measured by the phosphorylation rate, were also reduced after heroin self-administration, an effect that seemed more apparent in the protracted withdrawal group.ConclusionsThese results suggest that heroin self-administration under extended access conditions modifies the expression profile of activators and components of the mTOR complexes and show a putative irresponsive mTOR complex 2 after withdrawal from heroin use.

Metformin induces myeloma cells necrosis and apoptosis and it is considered for therapeutic use

Accumulating evidence, especially in solid tumor, indicated that metformin possessed the potential ability in the proliferation of cancer cells. However, its effects on myeloma cells were relatively rarely clarified. To evaluate the anti-cancer effects of metformin against dexamethasone-resistant and -sensitive myeloma cells. The effects of metformin on myeloma cell lines, including dexamethasone-resistant U266, H929, RPMI 8226 and dexamethasone-sensitive MM.1s, were investigated using the cell counting kit-8 assay for cell proliferation. Apoptosis, necrosis, cell cycle arrest, and cell death mechanisms were explored via flow cytometry (FCM) and Western blot. In addition, the anti-myeloma activity was evaluated in vivo via non-obese diabetic/severe combined immunodeficiency xenograft mouse models. Metformin inhibited proliferation in a dose and time-dependent manner in all the cell lines, while dexamethasone only affected the viability of MM1.s cells. The FCM detection displayed that metformin induced apoptosis in H929, RPMI8226 and MM.1s cells, while for U266 cells, it induced necrosis with Annexin V-/Propidium iodide+. The cell cycle assays showed that metformin arrested G0/G1 phase of H929 and MM.1s cells, or G2/M phase of RPMI8226 cells, but showed no effect on U226 cells. Western blotting analyses demonstrated that the apoptosis-related protein of cleaved caspase 3 was activated; the expressions of Mcl-1, IGF-1R, PI3K, pAKT, and pmTOR proteins were inhibited by metformin in H929, RPMI8226, and MM.1s cells. The necrosis-related protein of iNOS increased in U266 cells while metformin treated. In vivo assay indicated metformin decreased U266 and H929 growth in bone marrow, and thus prolonged mice survival. These data suggested that metformin inhibited the proliferation of myeloma cells via inducing necrosis and apoptosis. This finding indicated that metformin may be served as a potent adjuvant in treating multiple myeloma.

The Role of ARID1A in the Nonestrogenic Modulation of IGF-1 Signaling.

This study underscores the possibility of the pharmacologic modulation of the ARID1A factor to downregulate protumorigenic IGF-1 activity in patients with postmenopausal breast cancer undergoing aromatase inhibitor treatment.

IGF2BP2 promotes gastric cancer progression by regulating the IGF1R-RhoA-ROCK signaling pathway

BackgroundOur study aimed to probe the intrinsic and concrete molecular mechanism of IGF2 mRNA-binding protein 2 (IGF2BP2) in gastric cancer (GC). MethodsThe mRNA and protein expressions were assessed using qRT-PCR and western blot, respectively. CCK-8 assay was employed to determine cell proliferation. Levels of TNFα and IL-1β were analyzed using ELISA. Furthermore, cell apoptosis was evaluated using flow cytometry analysis. Cell migration and invasion were evaluated using Transwell assay. The experiment of tumor formation in nude mice was employed to analyze the effect of IGF2BP2 in regulating GC tumor growth and lung metastasis in vivo. Finally, the binding relationship between IGF1R and IGF2BP2 was verified using RIP and RNA pull down assays. ResultsIGF2BP2 was significantly elevated in both GC tissues and cells. Silencing of IGF2BP2 dramatically suppressed the inflammation, proliferation, migration and invasion, yet promoted cell apoptosis in vitro and in vivo. Furthermore, IGF2BP2, as a m6A reader, was proved to increase the expression of IGF1R by identifying m6A methylation modification sites in IGF1R mRNA, thus activating RhoA-ROCK pathway. Importantly, the anti-carcinogenic impacts of IGFBP2 silence were restrained by IGF1R overexpression, which was eliminated by the inactivation of RhoA-ROCK. ConclusionWe emphasized the oncogenic role of IGF2BP2 in gastric carcinogenesis and confirmed its activation is partly due to the activation of IGF1R-RhoA-ROCK signaling pathway. Our findings identified that IGF2BP2 might be a promising prognostic biomarker and provided clinical translational potential.

An ex vivo approach to understanding sex-specific differences in placental androgen signalling in the presence and absence of inflammation.

The mechanisms that contribute to continued male intrauterine growth in response to an adverse maternal environment, such as those brought on by maternal asthma, remain largely undefined but may, in part, be mediated by androgen-mediated signalling. We previously reported the expression of multiple AR protein isoforms in the human placenta and proposed the novel AR-45 isoform to be integral in mediating male-specific androgen-dependent signalling in the presence of maternal asthma. In the current study we have used an ex vivo approach to further understand sex-specific differences in placental androgen signalling in the presence and absence of inflammation using human term villous placental explants. Explants were cultured in the presence and absence of 0.1nM dihydrotestosterone (DHT), 1μg/ml lipopolysaccharide (LPS), or DHT+LPS for 24hr. Tissue was used for gene expression and subcellular AR protein isoform expression. Cytoplasmic and nuclear AR protein isoforms expression did not vary between culture conditions in either sex. AR-45 activity was upregulated in male placentae cultured in DHT, LPS and DHT+LPS only. There were no changes in the expression of androgen-mediated downstream targets in males in response to culture conditions, but females had significantly reduced IGF1R expression in response to LPS. Increased AR-45 activity in the presence of inflammation may drive continued male feto-placental growth via maintained expression of downstream growth targets. Our findings build on previous work suggesting an important role for AR-45 in regulating male-specific adaptations to placental inflammation and underscores the need to further characterise the function of this AR isoform.

Circular RNA circ_0001459 accelerates hepatocellular carcinoma progression via the miR-6165/IGF1R axis.

An increasing amount of evidence shows that circular RNAs (circRNAs) have critical effects on cancer progression and development; however, the biological function and potential molecular mechanism of circRNAs in hepatocellular carcinoma (HCC) are still unclear. CircRNA sequencing was used to identify differentially expressed circRNAs between HCC tissue and adjacent normal tissue. We found that circ_0001459 expression was significantly elevated in HCC tissue and cell lines. Furthermore, in vitro and in vivo functional experiments were carried out to detect the effects of circ_0001459 on HCC growth and metastasis. Knockdown of circ_0001459 significantly inhibited the proliferation, migration, and invasion of HCC cells, whereas upregulation of circ_0001459 had the opposite effect. Moreover, bioinformatics analysis, dual‐luciferase reporter assay, RNA immunoprecipitation, and fluorescence in situ hybridization assays were used to predict and verify the interaction between circ_0001459, miR‐6165, and the target gene IGF1R. Downregulation of circ_0001459 decreased IGF1R expression and inhibited epithelial‐to‐mesenchymal transition, which could be rescued by treatment with a miR‐6165 inhibitor. Mechanistically, we revealed that circ_0001459 could sponge miR‐6165 and induce the upregulation of its downstream target IGF1R, thus significantly promoting the progression of HCC. Therefore, circ_0001459 could be a new potential therapeutic target for HCC patients.

Intra-amniotic administration of l-glutamine promotes intestinal maturation and enteroendocrine stimulation in chick embryos

Initial nutritional stimulation is a key driving force for small intestinal maturation. In chick embryos, administration of l-glutamine (Gln) into the amniotic fluid stimulates early development of the small intestinal epithelium by promoting enterocyte differentiation. In this study, we evaluated the effects of intra-amniotic administration of Gln on enterocyte morphology and function, and elucidated a potential enteroendocrine pathway through which Gln stimulates small intestinal maturation. Our results show that Gln stimulation at embryonic day 17 significantly increased enterocyte and microvilli dimensions by 10 and 20%, respectively, within 48 h. Post-hatch, enterocytes and microvilli were 20% longer in Gln-treated chicks. Correspondingly, Gln stimulation significantly upregulated mRNA expression of brush border nutrient transporters PepT-1 and SGLT-1 and tight junction proteins TJP-1 and TJP-2, before and after hatch (P < 0.05). Since GLP-2 signaling from intestinal L-cells is associated with enterocyte growth, functionality and integrity, we examined the effects of Gln stimulation on mRNA expression of key hormones and receptors within this enteroendocrine pathway and found significant increases in GLP-2R, IGF-1 and IGF-1R expression before and after hatch (P < 0.05). In conclusion, our findings link primary nutrient stimulation in the developing small intestine with enterocyte morphological and functional maturation and enteroendocrine signaling.

Structure–activity relationships of pH-responsive and ionizable lipids for gene delivery

Ionizable lipids are the leading vectors for gene therapy. Understanding the effects of molecular structure on efficient gene delivery is one of the most important challenges for maximizing the utility of such lipid vectors. We synthesized an array of pH-responsive and ionizable lipids to investigate the relationship between lipid structure and activity. The optimized lipid (EDM) has double tertiary amines in the headgroup and an ester linker. EDM exhibited efficient DNA and siRNA delivery to, and gene silencing of, A549 cells. EDM has a pKa value of 6.67, which enabled it to quickly escape from the endosome after entering the cell; the ester linkages rapidly degraded and enabled gene release into the cytoplasm. EDM also delivered IGF-1R siRNA to inhibit tumor growth and induce cancer cell apoptosis by efficient inhibition of IGF-1R expression in mice. Our study on the structure–activity relationships of ionizable lipids will facilitate clinical applications.

MicroRNA-100 Reduced Fetal Bovine Muscle Satellite Cell Myogenesis and Augmented Intramuscular Lipid Deposition by Modulating IGF1R.

Previously, microRNA-100 (miR-100) and its putative mRNA target, insulin-like growth factor receptor-1 (IGF1R) were identified as differentially and inversely expressed in bovine longissimus dorsi (LD) muscles with divergent intramuscular fat (IMF) content by our group. While IGF1R signaling is implicated in myogenesis and muscle lipid metabolism, the underlying regulatory mechanisms are poorly understood. In the present study, we aimed to investigate the regulation of IGF1R by miR-100 during bovine muscle satellite cell (BMSC) myogenesis and lipid deposition. MiR-100 was confirmed to target the IGF1R 3′-untranslated region (3′-UTR) by luciferase reporter assay. Furthermore, expression of miR-100 and IGF1R was reciprocal during BMSC differentiation, suggesting a crosstalk between the two. Correspondingly, miR-100 mimic (agomiR) suppressed the levels of IGF1R, PI3K/AKT pathway signaling, myogenic gene MYOG, muscle structural components MYH7 and MYH8, whereas the inhibitor (antagomiR) had no clear stimulating effects. The IGF1R inhibitor (BMS-754807) curtailed receptor levels and triggered atrophy in muscle myotubes but did not influence miR-100 expression. AgomiR increased oleic acid-induced lipid deposition in BMSC myotubes supporting its involvement in intramuscular fat deposition, while antagomiR had no effect. Moreover, mitochondrial beta-oxidation and long-chain fatty acid synthesis-related genes were modulated by agomiR addition. Our results demonstrate modulatory roles of miR-100 in BMSC development, lipid deposition, and metabolism and suggest a role of miR-100 in marbling characteristics of meat animals and fat oxidation in muscle.

Does Sertraline Affect Hypothalamic Food Intake Peptides in the Rat Experimental Model of Chronic Mild Stress-Induced Depression?

Depression is a chronic, recurrent and life-threatening disease affecting approximately 15% of the world population. Depression is responsible for neuropathologies like decreased neurogenesis and increased dendritic atrophy. Antidepressant treatments increase hippocampal neurogenesis and neurotrophic factor expression. Based on this information, it was aimed to investigate effect of sertraline on depression in rats with chronic mild stress (CMS) model and to determine how it affects cell proliferation and hypothalamic peptide levels in hypothalamus. 56 adult male Wistar albino; control, depression(D), depression + sertraline, sertraline were divided into groups. Various stressors were applied to D for 30days. Open field test (OFT) and forced swimming test (FST) were conducted to check whether the animals were depressed. On the 16th day osmotic minipump was placed subcutaneously and sertraline (10mg/kg/day) was administered for 15days. Behavior tests were done. Hypothalamic peptide gene expression levels were analyzed by quantitative RT-PCR. Statistical evaluations were made using ANOVA. It caused a decrease in the percentage of movement in the D and control groups in the OFT, an increase in the immobility time in the D group in the FST, and an increase in the swimming behavior in the DS group. Animals did not show any anxiological behavior based on the elevated plus maze test results. CMS caused a decrease in GLUT2 and NPY gene expression in the hypothalamus of animals, an increase in POMC and FGFR2, and an increase in IGFIR and GLUT2 gene expression in the DS group. Sertraline has been shown to ameliorate the effects of CMS-induced depression. Sertraline is thought to have a positive regulatory effect on both the formation of neural precursor cells and the survival of newly formed neurons in the hypothalamus. Newly formed neurons in the hypothalamus express food intake-related NPY, POMC, GLUT2 neurons, and thus hypothalamic tanycytes may play a key role in the control of energy metabolism.

Thyroid-Stimulating Hormone Favors Runx2-Mediated Matrix Mineralization in HOS and SaOS2 Cells: An In Vitro and In Silico Approach.

Osteoporosis is a skeletal disease that is both systemic and silent characterized by an unbalanced activity of bone remodeling leading to bone loss. Rising evidences demonstrate that thyroid stimulating hormone (TSH) has an important role in the regulation on the metabolism of bone. However, TSH regulation on human osteoblast essential transcriptional factors has not been identified. Current study examined the role of TSH on human osteoblastic Runx2 expression and their functional genes by in vitro and in slico analysis. Human osteoblast like (HOS and SaoS-2) cells were cultured with DMEM and treated with hTSH at the concentration of 0.01 ng/mL and 10 ng/mL. After treatment, osteoblastic Runx2 and IGF-1R beta expression were studied using RT-PCR and western blot analysis. TSH treatment induced osteoblastic essential transcriptional factor, Runx2 in HOS and SaOS2 cells on 48 h duration and elevated the expression of IGF-IR β gene and Protein in SaoS-2 cells. TSH also promotes Runx2 responsive genes such as ALP, Collagen and osteocalcin in SaOS2 cells on day 2 to day 14 of 10 ng/mL of treatment and favors’ matrix mineralization matrix in these cells. In addition, TSH facilitated human osteoblastic cells to mineralize their matrix confirmed by day 21 of alizarin red calcium staining. In silico study was performed to check CREB and ELK1 interaction with Runx2. Results of in silico analysis showed that TSH mediated signalling molecules such as CREB and ELK1 showed interaction with Runx2 which involve in osteobalstic gene expression and differentiation. Present findings confirm that TSH promotes Runx2 expression, osteoblastic responsive genes and bone matrix formation.

Exosomes Secreted by Nucleus Pulposus Stem Cells Derived From Degenerative Intervertebral Disc Exacerbate Annulus Fibrosus Cell Degradation via Let-7b-5p

The pathogenesis of intervertebral disc degeneration (IDD) is complex and remains unclear. Nucleus pulposus stem cells (NPSCs) and annulus fibrosus cells (AFCs) play a critical role in the maintenance of intervertebral disc structure and function. Exosome-mediated miRNAs regulate cell proliferation, differentiation, apoptosis, and degradation. However, it is not clear whether the degenerative intervertebral disc-derived nucleus pulposus stem cells (D-NPSCs) can regulate the function of AFCs by delivering exosomes. Here, we show that exosomes secreted by nucleus pulposus stem cells derived from degenerative intervertebral disc (D-DPSC-exo) can exacerbate AFC degeneration via inhibiting cell proliferation, migration, matrix synthesis, and promoting apoptosis. Specifically, let-7b-5p was highly expressed in D-DPSC-exo. Transfection of let-7b-5p mimic was found to promote apoptosis and inhibit proliferation migration and matrix synthesis of AFCs. In addition, transfection with let-7b-5p inhibitor caused the effect of D-DPSC-exo on AFCs to be reversed. Furthermore, we found that D-DPSC-exo and let-7b-5p inhibited IGF1R expression and blocked the activation of the PI3K–Akt pathway. Results suggested that NPSC-exo exacerbated cell degeneration of AFCs via let-7b-5p, accompanied by inhibition of IGF1R expression, and PI3K–Akt pathway activation. Therefore, insights from this work may provide a clue for targeted molecular therapy of intervertebral disc degeneration.

Maternal VD3 supplementation during gestation improves intestinal health and microbial composition of weaning piglets.

Vitamin D3 (VD3) has been reported to improve the reproductive performance of sows. This study was conducted to investigate the long-term effect of maternal VD3 supplementation during gestation on the intestinal health of piglets. Twenty-three Landrace × Yorkshire gilts were randomly allocated into two groups to receive one of the following two diets during gestation: basal diet (CON group, 800 IU VD3 per kg diet, n = 12) and VD3 supplemented diet (VD3 group, 2000 IU VD3 per kg diet, n = 11). All sows were then fed with the same diet during lactation. Results showed that maternal VD3 supplementation during lactation tended to decrease (p = 0.08) the body weight loss of sows during lactation compared to the CON group. Besides, the relative length and weight of the small intestine (SI) and the villus height of the duodenum and ileum in weaning piglets were much higher (p < 0.05) in the VD3 group than those in the CON group, though their body weight was not changed. Meanwhile, maternal VD3 supplementation significantly upregulated the expression levels of IGF-1, IGF-2R, VDR, GLUT-2 and CAT1 in the duodenum (p < 0.05), and increased the expression levels of IGF-1, IGF-1R, IGF-2R, VDR, Occludin, ZO-1, MUC2, PEPT1 and CAT1 (p < 0.05) in the jejunum of suckling piglets compared with the CON group. Besides, the concentration of SigA in the jejunum of suckling piglets was higher (p < 0.05) in the VD3 group than that in the CON group. In addition, maternal VD3 supplementation significantly increased the contents of short chain fatty acids and the relative abundance of Lactobacillus and Faecalibacterium (p < 0.05) in the feces of weaning piglets compared to the CON group. Moreover, the relative abundance of unidentified_Lachnospiraceae in the feces of weaning piglets tended to be higher (p = 0.05), while that of unidentified_Spirochaetaceae was lower (p < 0.05) in the VD3 group than those in the CON group. Taken together, maternal VD3 supplementation during gestation could improve the intestinal function and microbiota in suckling piglets.

Effects of Growth-Related Genes on Body Measurement Traits in Wenshang Barred Chickens.

Body measurement traits (BMTs), which are classical quantitative traits of vital responses to body growth, have been studied in pigs, cattle, and sheep for several decades. In chickens, BMTs mainly cover body slope length, keel length, chest width, chest depth, tibia length, and tibia diameter; however, their genetic markers are yet to be considered. In this study, the Wenshang Barred chicken, a meat-egg-type native breed in China, was used to investigate the association between BMTs and the expression of growth-related genes, including GH, IGF1, IGF2, GHRL, IGF1R, IGFBP2, GHF-1, and TSHB. The results revealed that the single nucleotide polymorphism (SNP) rs3138025 in GH was significantly associated with keel length (P=0.0455 <0.05), rs313810945 in IGF2 was significantly correlated with chest width (P=0.0454 <0.05) and chest depth (P=0.0259 <0.05), and rs317298536 in TSHB significantly affected chest depth (P=0.0399 <0.05). The SNPs were associated with traits reflecting body size and were potentially involved in bone growth, which was consistent with studies in humans, rodents, and other vertebrate species. In addition, a borderline significant association was found between rs317298536 and body weight (P=0.0604). These polymorphic sites may be treated as candidate genetic markers in breeding programs involving Wenshang Barred chickens.

IRS1 expression in hippocampus is age-dependent and is required for mature spine maintenance and neuritogenesis

Insulin and insulin-like growth factor type I (IGF-1) play prominent roles in brain activity throughout the lifespan. Insulin/IGF1 signaling starts with the activation of the intracellular insulin receptor substrates (IRS). In this work, we performed a comparative study of IRS1 and IRS2, together with the IGF1 (IGF1R) and insulin (IR) receptor expression in the hippocampus and prefrontal cortex during development. We found that IRS1 and IRS2 expression is prominent during development and declines in the aged hippocampus, contrary to IR, which increases in adulthood and aging. In contrast, IGF1R expression is unaffected by age. Expression patterns are similar in the prefrontal cortex. Neurite development occurs postnatally in the rodent hippocampus and cortex, and it declines in the mature and aged brain and is influenced by trophic factors. In our previous work, we demonstrated that knockdown of IRS1 by shRNA impairs learning and reduces synaptic plasticity in a rat model, as measured by synaptophysin puncta in axons. In this study, we report that shIRS1 alters spine maturation in adult hilar hippocampal neurons. Lastly, to understand the role of IRS1 in neuronal neurite tree, we transfect shIRS1 into primary neuronal cultures and observed that shIRS1 reduced neurite branching and neurite length.Our results demonstrate that IRS1/2 and insulin/IGF1 receptors display different age-dependent expression profiles and that IRS1 is required for spine maturation, demonstrating a novel role for IRS1 in synaptic plasticity.