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2.
Transforming growth factor β (TGFβ) superfamily is evolutionarily conserved and plays fundamental roles in cell growth and differentiation. Mounting evidence supports its important role in female reproduction and development. TGFBs1-3 are founding members of this growth factor family, however, the in vivo function of TGFβ signaling in the uterus remains poorly defined. By drawing on mouse and human studies as a main source, this review focuses on the recent progress on understanding TGFβ signaling in the uterus. The review also considers the involvement of dysregulated TGFβ signaling in pathological conditions that cause pregnancy loss and fertility problems in women.  相似文献   

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Background

To induce peroxisomal proliferator-activated receptor α (PPARα) expression and increase milk fat utilization in pigs at birth, the effect of maternal feeding of the PPARα agonist, clofibrate (2-(4-chlorophenoxy)-2-methyl-propanoic acid, ethyl ester), on fatty acid oxidation was examined at full-term delivery (0 h) and 24 h after delivery in this study. Each group of pigs (n = 10) was delivered from pregnant sows fed a commercial diet with or without 0.8% clofibrate for the last 7 d of gestation. Blood samples were collected from the utero-ovarian artery of the sows and the umbilical cords of the pigs as they were removed from the sows by C-section on day 113 of gestation.

Results

HPLC analysis identified that clofibric acid was present in the plasma of the clofibrate-fed sow (~4.2 μg/mL) and its offspring (~1.5 μg/mL). Furthermore, the maternal-fed clofibrate had no impact on the liver weight of the pigs at 0 h and 24 h, but hepatic fatty acid oxidation examined in fresh homogenates showed that clofibrate increased (P < 0.01) 14C-accumulation in CO2 and acid soluble products 2.9-fold from [1-14C]-oleic acid and 1.6-fold from [1-14C]-lignoceric acid respectively. Correspondingly, clofibrate increased fetal hepatic carnitine palmitoyltransferase (CPT) and acyl-CoA oxidase (ACO) activities by 36% and 42% over controls (P < 0.036). The mRNA abundance of CPT I was 20-fold higher in pigs exposed to clofibrate (P < 0.0001) but no differences were detected for ACO and PPARα mRNA between the two groups.

Conclusion

These data demonstrate that dietary clofibrate is absorbed by the sow, crosses the placental membrane, and enters fetal circulation to induce hepatic fatty acid oxidation by increasing the CPT and ACO activities of the newborn.  相似文献   

5.
BackgroundPreconditioning with inflammatory stimuli is used to improve the secretion of anti-inflammatory agents in stem cells from variant species such as mouse, human, and dog. However, there are only few studies on feline stem cells.ObjectivesThis study aimed to evaluate the immune regulatory capacity of feline adipose tissue-derived (fAT) mesenchymal stem cells (MSCs) pretreated with interferon-gamma (IFN-γ).MethodsTo assess the interaction of lymphocytes and macrophages with IFN-γ-pretreated fAT-MSCs, mouse splenocytes and RAW 264.7 cells were cultured with the conditioned media from IFN-γ-pretreated MSCs.ResultsPretreatment with IFN-γ increased the gene expression levels of cyclooxygenase-2, indoleamine 2,3-dioxygenase, hepatocyte growth factor, and transforming growth factor-beta 1 in the MSCs. The conditioned media from IFN-γ-pretreated MSCs increased the expression levels of M2 macrophage markers and regulatory T-cell markers compared to those in the conditioned media from naive MSCs. Further, prostaglandin E2 (PGE2) inhibitor NS-398 attenuated the immunoregulatory potential of MSCs, suggesting that the increased PGE2 levels induced by IFN-γ stimulation is a crucial factor in the immune regulatory capacity of MSCs pretreated with IFN-γ.ConclusionsIFN-γ pretreatment improves the immune regulatory profile of fAT-MSCs mainly via the secretion of PGE2, which induces macrophage polarization and increases regulatory T-cell numbers.  相似文献   

6.
Estrogen action is mediated through several types of receptors (ERs), such as ERα, ERβ and putative membrane ERs. Oxytocin receptor (OTR) and ER expression levels in the rat uterus are regulated by estrogen; however, which types of ERs are involved has not been elucidated. This study examined OTR, ERα and ERβ levels in ovariectomized rats treated with 17β-estradiol (E2), an ERα agonist (PPT), an ERβ agonist (DPN) or estren (Es). E2 and PPT increased OTR mRNA levels and decreased ERα and ERβ mRNA levels 3 and 6 h posttreatment. DPN decreased ERα and ERβ mRNA levels at 3 and 6 h, while OTR mRNA levels increased at 3 h and decreased at 6 h. OTR mRNA levels increased 3 h after the Es treatment and then declined until 6 h. ERα and ERβ mRNA levels decreased by 3 h and remained low until 6 h posttreatment with Es. The ER antagonist ICI182,780 (ICI) suppressed the increases in OTR mRNA levels induced 3 h after the Es treatment. However, ICI and tamoxifen (Tam) had no significant effect on ERα and ERβ mRNA levels in the Es-treated or vehicle-treated group. In intact rats, proestrus-associated increases in OTR mRNA levels were antagonized by both ICI and Tam. However, decreases in ERα and ERβ mRNA levels were not antagonized by Tam and ICI, respectively. Therefore, uterine OTR gene expression is upregulated by estrogen through the classical nuclear (or non-nuclear) ERs, ERα and ERβ, while the levels of these ERs are downregulated by estrogen through multiple pathways including Es-sensitive nonclassical ERs.  相似文献   

7.
Hamster sperm hyperactivation is enhanced by progesterone, and this progesterone-enhanced hyperactivation is suppressed by 17β-estradiol (17βE2) and γ-aminobutyric acid (GABA). Although it has been indicated that melatonin also enhances hyperactivation, it is unknown whether melatonin-enhanced hyperactivation is also suppressed by 17βE2 and GABA. In the present study, melatonin-enhanced hyperactivation was significantly suppressed by 17βE2 but not by GABA. Moreover, suppression of melatonin-enhanced hyperactivation by 17βE2 occurred through non-genomic regulation via the estrogen receptor (ER). These results suggest that enhancement of hyperactivation is regulated by melatonin and 17βE2 through non-genomic regulation.  相似文献   

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9.
The present study aimed to investigate the effects of dietary pioglitazone hydrochloride (PGZ) and l-carnosine (LC) supplementation on the growth performance, meat quality, antioxidant status, and meat shelf life of yellow-feathered broiler chickens. Five hundred broiler chickens were randomly assigned into 4 experimental diets using a 2 × 2 factorial arrangement with 2 PGZ supplemental levels (0 and 15 mg/kg) and 2 LC supplemental levels (0 and 400 mg/kg) in basal diets for 28 d. The feed-to-gain ratio decreased whereas the average daily gain increased with PGZ supplementation. Greater dressing percentages, contents of intramuscular fat (IMF) in breast and thigh muscles, C18:3n-6, C18:1n-9 and monounsaturated fatty acid (MUFA) percentages of thigh muscle were observed with PGZ addition. Additionally, significant synergistic effects between PGZ and LC on the C18:1n-9 and MUFA contents were found. Supplementation with LC decreased drip loss, cooking loss and total volatile basic nitrogen, and increased the redness (a∗) value, the superoxide dismutase and glutathione peroxidase activities in thigh muscles. Moreover, the malondialdehyde content decreased when diets were supplemented with LC, and there was a synergistic effect between PGZ and LC. Additionally, the mRNA abundance of lipogenesis-related genes, such as peroxisome proliferator-activated receptor γ (PPARγ), PPARγ co-activator 1α and fatty acid-binding protein 3, increased with PGZ supplementation, and relevant antioxidation genes, such as nuclear factor erythroid-2-related factor 2 and superoxide dismutase 1, were enhanced with LC supplementation. In conclusion, the results indicated that the supplementation of PGZ and LC could improve the growth performance, antioxidant ability, IMF content, and meat shelf life of yellow-feathered broiler chickens.  相似文献   

10.
Weaning stress can cause tight junctions damage and intestinal permeability enhancement, which leads to intestinal imbalance and growth retardation, thereby causing damage to piglet growth and development. Spermine can reduce stress. However, the mechanism of spermine modulating the intestinal integrity in pigs remains largely unknown. This study aims to examine whether spermine protects the intestinal barrier integrity of piglets through ras-related C3 botulinum toxin substrate 1 (Rac1)/phospholipase C-γ1 (PLC-γ1) signaling pathway. In vivo, 80 piglets were categorised into 4 control groups and 4 spermine groups (10 piglets per group). The piglets were fed with normal saline or spermine at 0.4 mmol/kg BW for 7 h and 3, 6 and 9 d. In vitro, we investigated whether spermine protects the intestinal barrier after a tumor necrosis factor α (TNF-α) challenge through Rac1/PLC-γ1 signaling pathway. The in vivo study found that spermine supplementation increased tight junction protein mRNA levels and Rac1/PLC-γ1 signaling pathway gene expression in the jejunum of piglets. The serum D-lactate content was significantly decreased after spermine supplementation (P < 0.05). The in vitro study found that 0.1 μmol/L spermine increased the levels of tight junction protein expression, Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance, and decreased paracellular permeability (P < 0.05). Further experiments demonstrated that spermine supplementation enhanced the levels of tight junction protein expression, Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance, and decreased paracellular permeability compared with the NSC-23766 and U73122 treatment with spermine after TNF-α challenge (P < 0.05). Collectively, spermine protects intestinal barrier integrity through Rac1/PLC-γ1 signaling pathway in piglets.  相似文献   

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12.
F.R. Huang  Z.P. Zhan  J. Luo  S.W. Jiang  J. Peng   《Livestock Science》2008,119(1-3):194-201
The aim of the study was to investigate the effect of duration of feeding linseed (rich in n-3 PUFA) on peroxisome proliferator-activated receptor γ (PPARγ) and tumor necrosis factor (TNF-α) gene expression, and muscle mass of growing–finishing barrows. Two isoenergetic and isonitrogenous diets were formulated, and one of which was the basal diet and another one was the linseed diet including linseed at the level of 10%. Twenty-four Landrace × Yorkshire barrows weighing 35 ± 3.7 kg were randomly assigned to four treatments with six individuals per treatment. Pigs in treatment 1 (T1) fed the control diet throughout the experimental period, while pigs in T2, T3 and T4 fed the control diet except for 30, 60, and 90 d prior to slaughter when the linseed diet were fed. The experiment was conducted for 90 days. The longissimus muscle mass and each muscle mass in the hind leg were weighted. PPARγ and TNF-α mRNA expression levels in muscle, spleen and adipose tissue, and plasma concentrations of TNF-α data were measured and analyzed. The results showed that the longissimus muscle mass, quadriceps femoris muscle mass and semitendinosus muscle mass increased linearly (P < 0.01) as prolonged the time of feeding linseed diet. The expression of PPARγ in longissimus muscle and spleen increased (P < 0.01) linearly as prolonged the time of feeding linseed diet, while the expression of PPARγ in adipose tissue were not affected (P = 0.095). Duration of linseed addition linearly decreased (P < 0.01) TNF-α gene expression levels in the longissimus dorsi muscle, adipose and spleen, and serum concentration of TNF-α as well. The expression levels of PPARγ negatively correlated with the expression of TNF-α in muscle (R2 = 0.70, P < 0.001) and spleen (R2R2 = 0.77, P < 0.001) respectively. Likewise, PPARγ expression level in spleen (R2R2 = 0.59, P < 0.01) or muscle (R2R2 = 0.52, P < 0.05) negative correlated with serum TNF-α concentration, while there were significant quadratic relation between muscular PPARγ (R2R2 = 0.80, P < 0.01) or muscular TNF-α (R2R2 = 0.87, P < 0.01) expression and the longissimus dorsi muscle mass. These data suggested that duration of feeding linseed diet lead to a linear decrease of TNF-α gene expression, which may increase the muscle mass in growing–finishing barrows, at least in part, through a PPARγ-dependent mechanism.  相似文献   

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BackgroundNaringin and its aglycone naringenin are citrus-derived flavonoids with several pharmacological effects. On the other hand, the mechanism for the anti-diabetic effects of naringenin and naringin are controversial and remain to be clarified further.ObjectiveThis study examined the relationship between glucose uptake and AMP-activated protein kinase (AMPK) phosphorylation by naringenin and naringin in high glucose-treated HepG2 cells.MethodsGlucose uptake was measured using the 2-NBDG fluorescent D-glucose analog. The phosphorylation levels of AMPK and GSK3β (Glycogen synthase kinase 3 beta) were observed by Western blotting. Molecular docking analysis was performed to evaluate the binding affinity of naringenin and naringin to the γ-subunit of AMPK.ResultsThe treatment with naringenin and naringin stimulated glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Both flavonoids increased glucose uptake by promoting the phosphorylation of AMPK at Thr172 and increased the phosphorylation of GSK3β. Molecular docking analysis showed that both naringenin and naringin bind to the γ-subunit of AMPK with high binding affinities. In particular, naringin showed higher binding affinity than the true modulator, AMP with all three CBS domains (CBS1, 3, and 4) in the γ-subunit of AMPK. Therefore, both naringenin and naringin could be positive modulators of AMPK activation, which enhance glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells.ConclusionsThe increased phosphorylation of AMPK at Thr172 by naringenin and naringin might enhance glucose uptake regardless of insulin stimulation in high glucose treated HepG2 cells.  相似文献   

15.
To investigate 1α,25-(OH)2D3 regulation of matrix metalloproteinase-9 (MMP-9) protein expression during osteoclast formation and differentiation, receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) were administered to induce the differentiation of RAW264.7 cells into osteoclasts. The cells were incubated with different concentrations of 1α,25-(OH)2D3 during culturing, and cell proliferation was measured using the methylthiazol tetrazolium method. Osteoclast formation was confirmed using tartrate-resistant acid phosphatase (TRAP) staining and assessing bone lacunar resorption. MMP-9 protein expression levels were measured with Western blotting. We showed that 1α,25-(OH)2D3 inhibited RAW264.7 cell proliferation induced by RANKL and M-CSF, increased the numbers of TRAP-positive osteoclasts and their nuclei, enhanced osteoclast bone resorption, and promoted MMP-9 protein expression in a concentration-dependent manner. These findings indicate that 1α,25-(OH)2D3 administered at a physiological relevant concentration promoted osteoclast formation and could regulate osteoclast bone metabolism by increasing MMP-9 protein expression during osteoclast differentiation.  相似文献   

16.

Background

Transforming growth factor beta 1 (TGFβ1) is a pleiotropic cytokine that contributes to reparative skeletal remodeling by inducing osteoblast proliferation, migration, and angiogenesis. Organic bone matrix is the largest bodily reservoir for latent TGFβ1, and active osteoblasts express cognate receptors for TGFβ1 (TGFβRI and TGFβRII). During malignant osteolysis, TGFβ1 is liberated from eroded bone matrix and promotes local progression of osteotropic solid tumors by its mitogenic and prosurvival activities.

Hypothesis

Canine osteosarcoma (OS) cells will possess TGFβ1 signaling machinery. Blockade of TGFβ1 signaling will attenuate pro‐tumorigenic activities in OS cells. Naturally occurring primary OS samples will express cognate TGFβ1 receptors; and in dogs with OS, focal malignant osteolysis will contribute to circulating TGFβ1 concentrations.

Animals

Thirty‐three dogs with appendicular OS.

Methods

Expression of TGFβ1 and its cognate receptors, as well as the biologic effects of TGFβ1 blockade, was characterized in OS cells. Ten spontaneous OS samples were characterized for TGFβRI/II expressions by immunohistochemistry. In 33 dogs with OS, plasma TGFβ1 concentrations were quantified and correlated with bone resorption.

Results

Canine OS cells secrete TGFβ1, express cognate receptors, and TGFβ1 signaling blockade decreases proliferation, migration, and vascular endothelial growth factor secretion. Naturally occurring OS samples abundantly and uniformly express TGFβRI/II, and in OS‐bearing dogs, circulating TGFβ1 concentrations correlate with urine N‐telopeptide excretion.

Conclusions and Clinical Importance

Canine OS cells possess TGFβ1 signaling machinery, potentially allowing for the establishment of an autocrine and paracrine pro‐tumorigenic signaling loop. As such, TGFβ1 inhibitors might impede localized OS progression in dogs.  相似文献   

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BackgroundCompared to medium containing 108 mM sodium chloride (NaCl), in vitro maturation (IVM) using a simple medium with reduced (61.6 mM) NaCl increases the cytoplasmic maturation and embryonic development of pig oocytes.ObjectivesThis study determines the effect of a complex medium containing reduced NaCl on the IVM and embryonic development of pig oocytes.MethodsPig oocytes were matured in Minimum Essential Medium Eagle-alpha modification (αMEM) supplemented with 61.6 (61αMEM) or 108 (108αMEM) mM NaCl, and containing polyvinyl alcohol (PVA) (αMEMP) or pig follicular fluid (PFF) (αMEMF). Medium-199 (M199) served as the control for conventional IVM. Cumulus cell expansion, nuclear maturation, intra-oocyte glutathione (GSH) contents, size of perivitelline space (PVS), and embryonic development after parthenogenesis (PA) and somatic cell nuclear transfer (SCNT) were evaluated after IVM.ResultsRegardless of PVA or PFF supplementation, oocytes matured in 61αMEM showed increased intra-oocyte GSH contents and width of PVS (p < 0.05), as well as increased blastocyst formation (p < 0.05) after PA and SCNT, as compared to oocytes matured in 108αMEMP and M199. Under conditions of PFF-enriched αMEM, SCNT oocytes matured in 61αMEMF showed higher blastocyst formation (p < 0.05), compared to maturation in 108αMEMF and M199, whereas PA cultured oocytes showed no significant difference.ConclusionsIVM in αMEM supplemented with reduced NaCl (61.6 mM) enhances the embryonic developmental competence subsequent to PA and SCNT, which attributes toward improved oocyte maturation.  相似文献   

18.
BackgroundHypoxia causes oxidative stress and affects cardiovascular function and the programming of cardiovascular disease. Melatonin promotes antioxidant enzymes such as superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase.ObjectivesThis study aims to investigate the correlation between melatonin and hypoxia induction in cardiomyocytes differentiation.MethodsMouse embryonic stem cells (mESCs) were induced to myocardial differentiation. To demonstrate the influence of melatonin under hypoxia, mESC was pretreated with melatonin and then cultured in hypoxic condition. The cardiac beating ratio of the mESC-derived cardiomyocytes, mRNA and protein expression levels were investigated.ResultsUnder hypoxic condition, the mRNA expression of cardiac-lineage markers (Brachyury, Tbx20, and cTn1) and melatonin receptor (Mtnr1a) was reduced. The mRNA expression of cTn1 and the beating ratio of mESCs increased when melatonin was treated simultaneously with hypoxia, compared to when only exposed to hypoxia. Hypoxia-inducible factor (HIF)-1α protein decreased with melatonin treatment under hypoxia, and Mtnr1a mRNA expression increased. When the cells were exposed to hypoxia with melatonin treatment, the protein expressions of phospho-extracellular signal-related kinase (p-ERK) and Bcl-2-associated X proteins (Bax) decreased, however, the levels of phospho-protein kinase B (p-Akt), phosphatidylinositol 3-kinase (PI3K), B-cell lymphoma 2 (Bcl-2) proteins, and antioxidant enzymes including Cu/Zn-SOD, Mn-SOD, and catalase were increased. Competitive melatonin receptor antagonist luzindole blocked the melatonin-induced effects.ConclusionsThis study demonstrates that hypoxia inhibits cardiomyocytes differentiation and melatonin partially mitigates the adverse effect of hypoxia in myocardial differentiation by regulating apoptosis and oxidative stress through the p-AKT and PI3K pathway.  相似文献   

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The occurrence of bovine ketosis involves the accumulation of β-hydroxybutyric acid (BHBA), which contributes to the initiation and acceleration of hepatic metabolic stress and inflammation. Metformin has other beneficial effects apart from its medical intervention for diabetes, such as prevention of laminitis and hyper-triglyceridemic. AMPK maintains energy homeostasis and is the intracellular target of metformin action. This study aims to uncover the role of metformin in modulating BHBA-induced inflammatory responses through the activation of AMPK signaling. The hepatocytes were isolated from the liver tissue of mid-lactation multiparous Holstein cows (~160 d postpartum). Treatments were conducted as follows: treated with PBS for 18 h (control); pretreated with PBS for 12 h followed by treatment of 1.2 mM BHBA for 6 h (BHBA); pretreated with 1.5 mM or 3 mM metformin for 12 h followed by the BHBA treatment (1.2 mM) for 6 h (M(1.5)+B; M(3)+B). The inhibitor of AMPK, Compound C, at a concentration of 10 μM, was applied to substantiate the AMPK-dependent responses. RT-qPCR were applied for the mRNA expression while Western-blots and immunofluorescence were conducted for the target proteins expression. Among dose-dependent assays for BHBA, the concentration of BHBA at 1.2 mM activated NF-κB signaling by upregulating the expression of phosphorylated NF-κB and pro-inflammatory cytokines compared with the control cells (P < 0.05). Along with the upregulation of phosphorylated AMPKα and ACCα, metformin at 1.5 and 3 mM inactivated NF-κB signaling components (p65 and IκBα) and the inflammatory genes (TNFA, IL6, IL1B and COX-2) which were activated by BHBA. Additionally, BHBA inhibited cells staining intensity in EdU assay were increased by pretreatment with metformin. The activation of AMPK resulted in the increased gene and protein expression of SIRT1, along with the deacetylation of H3K9 and H3K14. However, the AMPK inhibitor compound C blocked this effect. Compared with BHBA treated cells, the protein expression of COX-2 and IL-1β were decreased by the pretreatment with metformin, and the inhibitory effect of metformin was released by compound C. The bound of NF-κB onto IL1B promoter displayed higher in BHBA group and this was suppressed by pretreatment with metformin (P < 0.05). Altogether, metformin attenuates the BHBA-induced inflammation through the inactivation of NF-κB as a target for AMPK/SIRT1 signaling in bovine hepatocytes.  相似文献   

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