scholarly journals Thymic Stromal Lymphopoietin Signaling Pathway Inhibition Attenuates Airway Inflammation and Remodeling in Rats with Asthma

2018 ◽  
Vol 47 (4) ◽  
pp. 1482-1496 ◽  
Author(s):  
Zhe  Cheng ◽  
Xi Wang ◽  
Ling-Ling Dai ◽  
Liu-Qun Jia ◽  
Xiao-Gang Jing ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Signaling Pathway ◽  
Airway Remodeling ◽  
Quantitative Polymerase Chain Reaction ◽  
Thymic Stromal Lymphopoietin ◽  
Collagen I ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Protein Levels ◽  
Ifn Γ

Background/Aims: Thymic stromal lymphopoietin (TSLP) is a cytokine that plays diverse roles in the regulation of immune responses. However, a detailed understanding of the TSLP signaling pathway in asthma remains elusive. In this study, we aimed to investigate the role of the TSLP signaling pathway in asthma and its effect on airway inflammation and remodeling. Methods: Forty Sprague Dawley (SD) rats were evenly classified into control, asthma, IgG2a mAb and anti-TSLP mAb groups. Ovalbumin (OVA)-induced asthma models were successfully established. Blood, bronchoalveolar lavage fluid (BALF) and lung tissue samples were prepared. Total BALF leukocytes were counted, and the proportions of different leukocyte types were determined. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to determine the mRNA and protein levels of TSLP, OX40L, α-smooth muscle actin (α-SMA, a marker of airway remodeling in asthma) and collagen I in the plasma. Enzyme-linked immunosorbent assay (ELISA) was carried out to measure the concentrations of TSLP, OX40L, and other inflammatory factors, such as interferon (IFN)-γ, interleukin (IL)-4, IL-5 and IL-13, in the plasma. Results: Compared with the control group, there were more leukocytes, increased EOS and LYM proportions, higher Underwood and PAS scores, increased WTt, WTm, WAt/A0, WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and collagen I mRNA and protein levels, and higher SLP, OX40L, IL-4, IL-5 and IL-13 levels, but lower MON proportions and IFN-γ levels in the asthma and IgG2a mAb groups. Compared with the asthma and IgG2a mAb groups, there were less leukocytes, decreased EOS and LYM proportions, lower Underwood and PAS scores, decreased WTt, WTm, WAt/A0, WAm/WAt, WTt/R0, WTm/WTt, TSLP, OX40L, a-SMA and Collagen I mRNA and protein levels, and lower levels of SLP, OX40L, IL-4, IL-5 and IL-13, but higher MON proportions and IFN-γ levels in the anti-TSLP mAb group. WTm and WTt were positively associated with the TSLP, OX40L, α-SMA and collagen-I levels in the rat lung tissues. Conclusion: The results indicate that TSLP may be an important contributor for asthma development as TSLP signaling blockade attenuates airway inflammation and remodeling in asthmatic rats.

scholarly journals Novel Compound Q-1 Alleviates Type II Collagen-Induced Arthritis in Rats through the NF-κB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ting Xu ◽  
Jia-Chen Guo ◽  
Sha-Sha Wu ◽  
Yan Wang ◽  
Xiao-Long Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ankle Joint ◽  
Liver Homogenate ◽  
Type Ii Collagen ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Type Ii ◽  
Collagen Induced Arthritis ◽  
Protein Levels

Background. Q-1 is a novel compound extracted from the Miao medicine Tiekuaizi. Although Q-1 is known to be a coumarin derivative, its structure has not been deposited in the ACX library. Our previous study showed that Q-1 inhibits the activity of inflammatory cells. This study explores the efficacy of Q-1 in regulating rheumatoid arthritis (RA). The findings show that Q-1 acts through the NF-κB signaling pathway. Methods. The effects of Q-1 were explored using a bovine type II collagen-induced arthritis (CIA) rat model. The CIA rats were intragastrically administered with high (30 mg·kg−1) or low (15 mg·kg−1) doses of Q-1. The control group was administered with an equal volume of drinking water, while the positive control group was administered with Tripterygium glycoside (9.45 mg·kg−1) for 28 consecutive days. The arthritis indices and ankle joint swelling rates were determined. The levels of IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1) in serum and sialic acid (SA) in liver homogenate were determined by enzyme-linked immunosorbent assay (ELISA). The pathological features of the ankle joint were analyzed by hematoxylin and eosin (HE) staining. The IκB, P-IκB, P65, and P-P65 protein levels in synovial tissue were assayed by western blotting. Results. The arthritis index, ankle joint swelling rate, IL-1β, IL-6, and MCP-1 levels in serum, SA level in liver tissue, and IκB, P-IκB, P65, and P-P65 protein levels in synovial tissues were significantly higher ( P < 0.01 ) in the CIA model compared to the control group. RA was successfully replicated by the CIA model, as shown by the joint swelling results and histopathological sections of the ankle. Notably, all the above indicators decreased significantly ( P < 0.01 ) after treatment with Q-1 compared to the model. In addition, animals treated with Q-1 showed lower inflammation in the ankle joints than the model rats. Conclusion. The findings indicate that Q-1 effectively inhibited RA in rats by downregulating IκB, P-IκB, P65, and P-P65, inhibiting the excessive release of inflammatory factors, and inhibiting the overactivation of the NF-κB signaling pathway.

scholarly journals Exploratory field study on the effects of porcine circovirus 2 (PCV-2) sow vaccination at different physiological stages mimicking blanket vaccination

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Patricia Pleguezuelos ◽  
Marina Sibila ◽  
Raúl Cuadrado ◽  
Rosa López-Jiménez ◽  
Diego Pérez ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Negative Control Group ◽  
Negative Control ◽  
Late Gestation ◽  
Antibody Detection ◽  
Porcine Circovirus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Physiological Status ◽  
Porcine Circovirus 2

Abstract Background The objective of the present study was to explore the benefits of Porcine circovirus 2 (PCV-2) blanket vaccination in a sow herd on productive parameters, PCV-2 infection and immune status in sows and their progeny. For this purpose, 288 sows were distributed among four balanced experimental groups. One group remained as negative control group and the other three received 1 mL of PCV-2 Ingelvac Circoflex® intramuscularly at different productive cycle moments: before mating, mid gestation (42–49 days post-insemination) or late gestation (86–93 days post-insemination); phosphate buffered saline (PBS) was used as negative control item. Reproductive parameters from sows during gestation and body weight of their progeny from birth to weaning were recorded. Additionally, blood was collected from sows at each vaccination time and piglets at 3 weeks of age. Moreover, up to 4 placental umbilical cords (PUC) per sow were taken at peri-partum. Sera from sows and piglets were analysed for PCV-2 antibody detection using an enzyme-linked immunosorbent assay (ELISA). Sera from sows and PUC were tested to quantify viraemia using a real time quantitative polymerase chain reaction (qPCR) assay. Results Globally, results indicated that vaccinated sows showed heavier piglets at birth and at weaning, less cross-fostered piglets, lower viral load at farrowing as well as in PUC, and higher antibody levels at farrowing, compared to non-vaccinated ones. When all groups were compared among them, sows vaccinated at mid or late gestation had heavier piglets at birth than non-vaccinated sows, and lower proportion of PCV-2 positive PUC. Also, cross-fostering was less frequently practiced in sows vaccinated at pre-mating or mid gestation compared to non-vaccinated ones. Conclusions In conclusion, the present study points out that PCV-2 sow vaccination at different time points of their physiological status (mimicking blanket vaccination) offers benefits at production and serological and virological levels.

scholarly journals miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 274-283
Author(s):  
Peng Yang ◽  
Jianhua Han ◽  
Shigeng Li ◽  
Shaoning Luo ◽  
Xusheng Tu ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Aberrant Expression ◽  
Protein Levels ◽  
Apoptosis And Inflammation ◽  
Hk2 Cells

Abstract Background Sepsis is a systemic inflammatory response that can lead to the dysfunction of many organs. The aberrant expression of miRNAs is associated with the pathogenesis of sepsis. However, the biological functions of miR-128-3p in sepsis remain largely unknown, and its mechanism should be further investigated. This study aimed to determine the regulatory network of miR-128-3p and TGFBR2 in lipopolysaccharide (LPS)-induced sepsis. Methods The expression levels of miR-128-3p and transforming growth factor beta receptors II (TGFBR2) were detected by quantitative polymerase chain reaction (qPCR). The protein levels of TGFBR2, Bcl-2, Bax, cleaved caspase 3, Smad2, and Smad3 were measured by western blot. Cell apoptosis was analyzed by flow cytometry. Cytokine production was detected by enzyme-linked immunosorbent assay (ELISA). The binding sites of miR-128-3p and TGFBR2 were predicted by Targetscan online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results The level of miR-128-3p was decreased, and TGFBR2 expression was increased in serum samples of sepsis patients and LPS-induced HK2 cells. Overexpression of miR-128-3p or knockdown of TGFBR2 ameliorated LPS-induced inflammation and apoptosis. Moreover, TGFBR2 was a direct target of miR-128-3p, and its overexpression reversed the inhibitory effects of miR-128-3p overexpression on inflammation and apoptosis in LPS-induced HK2 cells. Besides, overexpression of miR-128-3p downregulated TGFBR2 to suppress the activation of the Smad signaling pathway. Conclusion miR-128-3p could inhibit apoptosis and inflammation by targeting TGFBR2 in LPS-induced HK2 cells, which might provide therapeutic strategy for the treatment of sepsis.

scholarly journals The Absence of TLR4 Prevents Fetal Brain Injury in the Setting of Intrauterine Inflammation

2018 ◽  
Vol 26 (8) ◽  
pp. 1082-1093 ◽  
Author(s):  
Natalia M. Tulina ◽  
Amy G. Brown ◽  
Guillermo O. Barila ◽  
Michal A. Elovitz
Keyword(s):  
Brain Injury ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Fetal Brain ◽  
Notch Signaling Pathway ◽  
Mouse Strains ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway

Background: Exposure to intrauterine inflammation during pregnancy is linked to brain injury and neurobehavioral disorders in affected children. Innate immunity, specifically Toll-like receptor (TLR) signaling pathways are present throughout the reproductive tract as well as in the placenta, fetal membranes, and fetus. The TLR pathways are mechanistically involved in host responses to foreign pathogens and may lead to brain injury associated with prenatal inflammation. Objective: We aimed to determine whether the activation of the TLR4 signaling pathway, in the mother and fetus, is critical to fetal brain injury in the setting of intrauterine inflammation. Methods: A mini-laparotomy was performed on time pregnant C57B6 mice and 2 knockout mouse strains lacking the function of the Tlr4 and Myd88 genes on embryonic day 15. Intrauterine injections of Escherichia coli lipopolysaccharide or saline were administered as described previously. Dams were killed 6 hours postsurgery, and placental, amniotic fluid, and fetal brain tissue were collected. To assess brain injury, quantitative polymerase chain reaction (qPCR) analysis was performed on multiple components of the NOTCH signaling pathway, including Hes genes. Interleukin (IL) IL6, IL1β, and CCL5 expression was assessed using qPCR and enzyme-linked immunosorbent assay. Results: Using an established mouse model of intrauterine inflammation, we demonstrate that the abrogation of TLR4 signaling eliminates the cytokine response in mother and fetus and prevents brain injury associated with increased expression of transcriptional effectors of the NOTCH signaling pathway, Hes1 and Hes5. Conclusions: These data show that the activation of the TLR4 signaling pathway is necessary for the development of fetal brain injury in response to intrauterine inflammation.

scholarly journals Glutamine modifies immune responses of mice infected with porcine circovirus type 2

2013 ◽  
Vol 110 (6) ◽  
pp. 1053-1060 ◽  
Author(s):  
Wenkai Ren ◽  
Yinghui Li ◽  
Xinglong Yu ◽  
Wei Luo ◽  
Gang Liu ◽  
...  
Keyword(s):  
Experimental Period ◽  
Porcine Circovirus Type ◽  
Virus Genome ◽  
Porcine Circovirus Type 2 ◽  
Porcine Circovirus ◽  
Glutamine Supplementation ◽  
Control Group ◽  
Protein Levels ◽  
Ifn Γ

The present study was conducted to evaluate the immune-enhancing effects of dietaryl-glutamine supplementation in porcine circovirus type 2 (PCV2)-infected mice, and to examine the clearance effects of glutamine against PCV2 in experimentally infected mice. A total of sixty Kunming female mice were infected with PCV2 at a dose of 100 TCID50(50 % tissue culture infection dose) by intraperitoneal injection after 2 weeks of dietaryl-glutamine supplementation orl-alanine supplementation (as the control (isonitrogenous) group). The measured variables on 3rd, 5th, 7th, 9th and 11th d post-infection (dpi) included: (1) PCV2 virus loaded in the liver, spleen, heart, lung, kidney, ovary and serum was determined by real-time PCR; (2) IL-2, IL-6, IL-10, interferon (IFN)-α, IFN-γ and C-reactive protein levels in serum were measured by ELISA; (3) serum total superoxide dismutase activity was measured spectrophotometrically at 550 nm absorbance. Dietaryl-glutamine supplementation significantly increased serum IL-2 levels on the 3rd (P< 0·01), 5th (P< 0·01), 7th (P< 0·05) and 9th dpi, significantly (P< 0·05) increased serum IL-6 levels on 3rd dpi, significantly (P< 0·05) increased serum IFN-γ levels on the 9th and 11th dpi and significantly decreased (P< 0·01) serum IL-10 levels on the 9th and 11th dpi, compared with those in the control group. Meanwhile, the PCV2 virus genome was detected sporadically throughout the experimental period in both groups. Taken together, the present results suggest that dietaryl-glutamine supplementation enhances immune function in PCV2-infected mice.

ALK7 Inhibition Protects Osteoblast Cells Against High Glucose-induced ROS Production via Nrf2/HO-1 Signaling Pathway

2021 ◽  
Vol 21 ◽  
Author(s):  
Zhen Zhao ◽  
Yu Lu ◽  
Huan Wang ◽  
Xiang Gu ◽  
Luting Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Signaling Pathway ◽  
High Glucose ◽  
Collagen I ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Ros Production ◽  
Alizarin Red

Background: Some studies demonstrated that under high-glucose (HG) condition, osteoblasts develop oxidative stress, which will impair their normal functions. The effects of activin receptor-like kinase 7 (ALK7) silencing on HG-induced osteoblasts remained unclear. Objective: The aim of this study was to explore the effect of ALK7 on HG-induced osteoblasts. Methods: MC3T3-E1 cells were treated with different concentrations of HG (0, 50, 100, 200 and 300mg/dL), and the cell viability was detected using cell counting kit-8 (CCK-8). HG-treated MC3T3-E1 cells were transfected with siALK7 or ALK7 overexpression plasmid or siNrf2, and then the viability and apoptosis were detected by CCK-8 and flow cytometry. The levels of reactive oxygen species (ROS), collagen I and calcification nodule were determined by oxidative stress kits, Enzyme-linked immunosorbent assay and Alizarin red staining. The expressions of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and osteoblast-associated genes were determined by quantitative real-time PCR (qRT-PCR) and Western blot. Results: Cell viability was reduced with HG treatment. Silencing ALK7 inhibited the effect of HG on increasing cell apoptosis and ROS production, reduced cell viability, mineralized nodules, and downregulated collagen I and osteoblast-associated genes expression in MC3T3-E1 cells. ALK7 silencing activated the Nrf2/HO-1 signaling pathway by affecting expressions of HO-1 and Nrf2. ALK7 overexpression had the opposite effects. In addition, siNrf2 partially reversed the effects of ALK7 silencing on HG-induced MC3T3-E1 cells. Conclusion: ALK7 silencing protected osteoblasts under HG condition possibly through activating the Nrf2/HO-1 pathway.

scholarly journals Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Weitao Ji ◽  
Hongyun Shi ◽  
Hailin Shen ◽  
Jing Kong ◽  
Jiayi Song ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Acute Liver Injury ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Klf4 Expression ◽  
Mrna And Protein Expression

Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

scholarly journals Relationship between serum-based biomarkers & Magnetic Resonance Imaging measures following mild traumatic brain injury in collegiate athletes post return to play

Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S25.1-S25
Author(s):  
Taylor Susa ◽  
Marguerite Moore ◽  
Joshua Carlson
Keyword(s):  
Gray Matter Volume ◽  
Collegiate Athletes ◽  
Positive Association ◽  
Time Frame ◽  
Return To Play ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Serum Samples ◽  
Protein Levels ◽  
Mri Scans

ObjectiveThis study analyzed MRI and serum samples from 30 participants across two groups to explore the relationship between protein levels and MRI scans in post return-to-play collegiate athletes following concussion.BackgroundRecently, there has been an increase in concussion research on their effects on different protein levels in serum (a derived portion of blood) between concussed and control groups. Recent research examining serum biomarkers in concussion have found elevated levels of many proteins, but overall have mixed results in correlation with MRI. However, these studies have not focused on the lingering effects that exist in post return-to-play.Design/MethodsThe first group (n = 15) consisted of recently cleared to return-to-play collegiate athletes after experiencing a sports-related concussion. The second group (n = 15) was collegiate athlete controls matched on age, sex, and sport. Serum samples were collected to assess the levels of proteins following post return-to-play. These proteins were evaluated using Enzyme-Linked Immunosorbent Assay kits (ELIASA).ResultsAn overall BDNF effect was observed between groups (p < 0.05), the concussed group exhibited significantly higher levels of serum BDNF compared to the control group. A positive association between BDNF and gray matter volume (GMV) was observed at a 250 voxel cluster level in both the right (pFDR = 0.015) and left cerebellum region (pFDR = 0.045) across groups. A negative association between BDNF and GMV in both groups was observed in the brainstem (p = 0.029) and the precuneus (p = 0.017) areas. A differential relationship between group and BDNF on GMV was observed (p = 0.022) in the prefrontal cortex.ConclusionsPrevious research has not examined the post return-to-play effects in neuroplasticity specific proteins, nor the time frame of injury in comparison to controls with MRI. Serum-based biomarkers and MRI grant a better depiction of what is occurring during post return-to-play.

scholarly journals Honeysuckle extract relieves ovalbumin-induced allergic rhinitis by inhibiting AR-induced inflammation and autoimmunity

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Bin Lin ◽  
Bijuan Cai ◽  
Huige Wang
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Inflammatory Reaction ◽  
Lavage Fluid ◽  
Nasal Lavage ◽  
Autoimmune Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protein Levels ◽  
Nasal Lavage Fluid ◽  
Ifn Γ

Abstract Honeysuckle has antiviral, antioxidative and anti-inflammatory properties. Allergic rhinitis (AR) is induced by immunoglobulin E (IgE)-mediated inflammatory reaction. Our study investigates whether honeysuckle extract (HE) has therapeutic effect on AR. An AR model of mice was established by ovalbumin (OVA). Hematoxylin–Eosin staining was used to assess nasal mucosa damage. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum histamine, IgE and interleukin (IL)-2, IL-4, IL-17 and interferon-γ (IFN-γ) from nasal lavage fluid. Western blot was carried out to analyze the protein level from nasal mucosa tissue. We found that HE not only decreased nasal rubbing and sneezing in AR mice, but also reduced AR-induced damage to nasal mucosa. Moreover, HE lowered the levels of serum IgE and histamine and inhibited IL-4 and IL-17 levels from AR mice but raised IL-2 and IFN-γ levels in AR-induced nasal lavage fluid. Our results also showed that HE elevated the protein levels of forkhead box P3 (Foxp3) and T-box transcription factor (T-bet) in AR-induced nasal mucosa tissue, whereas it inhibited signal transducer and activator of transcription (STAT) 3 and GATA binding protein 3 (GATA-3) protein levels. By regulating AR-induced inflammatory reaction and autoimmune response, HE also relieved OVA-induced AR. Thus, HE could be used as a potential drug to treat AR.

scholarly journals Liraglutide Promotes Osteoblastic Differentiation in MC3T3-E1 Cells by ERK5 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yue Sun ◽  
Yuzhen Liang ◽  
Zhengming Li ◽  
Ning Xia
Keyword(s):  
Signaling Pathway ◽  
Osteoblastic Differentiation ◽  
Control Group ◽  
Activity Levels ◽  
Expression Levels ◽  
Protein Levels ◽  
Proliferation And Differentiation ◽  
Glucagon Like Peptide 1 ◽  
Differentiation And Proliferation

Liraglutide is a glucagon-like peptide-1 analogue widely used in the treatment of type 2 diabetes mellitus. However, the effects of liraglutide on osteoblast proliferation and differentiation in MC3T3-E1 cells have not been fully elucidated. In the present study, the promoting effects of liraglutide were investigated in MC3T3-E1 cells. The results indicated that cell viability was affected following the treatment of the cells with different concentrations of liraglutide (0, 10, 100, and 1000 nM) at different time periods of culture (24, 48, and 72 h). Moreover, the activity levels of alkaline phosphatase and the number of mineralized nodules in MC3T3-E1 cells were significantly increased following treatment with 100 nM liraglutide. The mRNA and protein levels of Col-1, OPG, and OCN in MC3T3-E1 cells were also markedly increased following 100 nM liraglutide treatment compared with those of the control group. The expression levels of the ERK5 signaling pathway key proteins (MEK5, p-ERK5, ERK5, and NUR77) were increased following liraglutide treatment in MC3T3-E1 cells, and the gene expression levels of the ERK5 signaling pathway were also elevated. Moreover, the ERK5 inhibitor XMD8-92 significantly decreased the expression levels of p-ERK5 and NUR77 as well as the proliferation of osteoblasts. However, these changes could be rescued by liraglutide to some extent. Therefore, these results revealed that liraglutide may promote osteoblastic differentiation and proliferation in MC3T3-E1 cells via the activation of the ERK5 signaling pathway.

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