Corydalis Saxicola Bunting Total Alkaloids Inhibits Paclitaxel-Induced Peripheral Neuropathy By Regulating PKCε-TRPV1 and p38 MAPK-TRPV1 Signaling Pathways

2021 ◽  
Author(s):  
chu xue ◽  
Si-Xue Liu ◽  
Jie Hu ◽  
Jin Huang ◽  
Hong-Min Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Peripheral Neuropathy ◽  
Protein Expression ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Cell Model ◽  
Mrna Levels ◽  
Drg Neurons ◽  
Total Alkaloids ◽  
Tnf Α

Abstract Background: Corydalis saxicola Bunting, a traditional Chinese medicine, has been proven to work well in anti-inflammation, blood circulation improvement, hemostasis, analgesia. This study was designed to observe the effects and potential mechanism of Corydalis saxicola Bunting total alkaloids (CSBTA) on paclitaxel-induced peripheral neuropathy (PIPN). Materials and methods: Following 4 times intraperitoneal injections of paclitaxel (2 mg/kg) and intragastrically (i.g.) administrated at 30 or 120 mg/kg CSBTA, mechanical and thermal allodynia and hyperalgesia in rats were tested. After 40 days, serum was collected for the detection of PGE2, TNF-α, and IL-1β by ELISA. The L4-L6 segment spinal cord, DRG, and plantar skin were harvested, and protein and gene expression of CGRP, SP, TRPV1, p38, and PKCε were analyzed by Western-blot or RT-qPCR. Parallelly, the PIPN cell model was also established in primary DRG neurons by paclitaxel stimulation (300 nM, 5 d). We examined PGE2, TNF-α and CGRP mRNA levels, and the protein expression on the PKCε-TRPV1 and p38 MAPK-TRPV1 pathways in PIPN cell model with or without CSBTA (25 μg/ml and 50 μg/ml). Results: The results showed that CSBTA effectively ameliorated allodynia and hyperalgesia in PIPN rats, regulated the contents of cytokines and neuropeptides in different tissues and cell models. CSBTA significantly decreased the protein expression of PKCε-TRPV1 and p38 MAPK-TRPV1 signaling pathways in the spinal cord and DRG tissues in the PIPN animal model and primary DRG neurons. Conclusion: Therefore, CSBTA has a perspective therapeutic effect on the treatment of paclitaxel-induced peripheral neuropathy.

scholarly journals Corydalis saxicola Bunting total alkaloids attenuate paclitaxel-induced peripheral neuropathy through PKCε/p38 MAPK/TRPV1 signaling pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Chu Xue ◽  
Si-Xue Liu ◽  
Jie Hu ◽  
Jin Huang ◽  
Hong-Min Liu ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Cell Model ◽  
Mrna Levels ◽  
Drg Neurons ◽  
Total Alkaloids ◽  
Tnf Α

Abstract Background Corydalis saxicola Bunting, affiliated with the Papaveraceae Juss., has been proven to work well in anti-inflammation, hemostasis, and analgesia. This study was designed to observe the effect and potential mechanism of Corydalis saxicola Bunting total alkaloids (CSBTA) on paclitaxel-induced peripheral neuropathy (PIPN). Materials and methods Rats were injected 2 mg/kg paclitaxel 4 times and administrated with 30 or 120 mg/kg CSBTA. Mechanical and thermal allodynia and hyperalgesia were tested. After 40 days, serum was collected to detect PGE2, TNF-α, and IL-1β by ELISA. The L4-L6 segment spinal cord, DRG, and plantar skin were harvested, and Western-blot or RT-qPCR analyzed protein and gene levels of pro-inflammatory cytokines, p38 MAPK, PKCε, and TRPV1. The PIPN cell model was established with paclitaxel (300 nM, 5 d) in primary DRG neurons. We examined the effect of CSBTA (25 μg/ml or 50 μg/ml) by measuring the mRNA levels in PGE2, TNF-α and CGRP, and the protein expression on the PKCε/p38 MAPK/TRPV1 signaling pathway in the PIPN cell model. Results The results showed that CSBTA effectively ameliorated allodynia and hyperalgesia, and regulated cytokines' contents (PGE2, TNF-α, and IL-1β) and neuropeptides (CGRP and SP) in different tissues in vivo. In addition, CSBTA significantly decreased cytokine gene levels of DRG neurons (PGE2, TNF-α, and CGRP) and the protein expressions of PKCε/p38 MAPK/TRPV1 signaling pathway in vivo and in vitro. Conclusion Therefore, CSBTA has a perspective therapeutic effect on the treatment of paclitaxel-induced peripheral neuropathy.

Interleukin-1α stimulates proinflammatory cytokine expression in human cardiac myofibroblasts

2009 ◽  
Vol 297 (3) ◽  
pp. H1117-H1127 ◽  
Author(s):  
Neil A. Turner ◽  
Anupam Das ◽  
Philip Warburton ◽  
David J. O'Regan ◽  
Stephen G. Ball ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Proinflammatory Cytokines ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Tnf Α ◽  
Interleukin 1Α ◽  
Cardiac Myofibroblasts

Cardiac myofibroblasts (CMF) play a key role in infarct repair and scar formation following myocardial infarction (MI) and are also an important source of proinflammatory cytokines. We postulated that interleukin-1α (IL-1α), a potential early trigger of acute inflammation post-MI, could stimulate human CMF to express additional proinflammatory cytokines. Furthermore, we hypothesized that these effects may be modulated by the anti-inflammatory cytokine interleukin-10 (IL-10). Human CMF were cultured from atrial biopsies from multiple patients. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cardiotrophin-1 (CT-1) mRNA expression and secretion were measured using quantitative real-time RT-PCR and enzyme-linked immunosorbent assay. IL-1α (0.001–10 ng/ml, 0–6 h) stimulated IL-1β, TNF-α, and IL-6 mRNA expression with distinct temporal and concentration profiles, resulting in increased cytokine secretion. The response to IL-1α was much greater than with TNF-α. Neither IL-1α nor TNF-α treatment modulated CT-1 mRNA expression. Immunoblotting with phosphospecific antibodies revealed that IL-1α stimulated the extracellular signal-regulated kinase (ERK)-1/2, p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B (Akt), and nuclear factor (NF)-κB signaling pathways. Pharmacological inhibitor studies indicated roles for PI 3-kinase/Akt and NF-κB pathways in mediating IL-1β expression, and for NF-κB and p38 MAPK pathways in mediating TNF-α expression. IL-1α-induced IL-6 mRNA expression was reduced by p38 MAPK inhibition, but increased by ERK and JNK pathway inhibitors. IL-10 produced a consistent but modest reduction in IL-1α-induced IL-6 mRNA levels (not IL-1β or TNF-α), but this was not reflected by reduced IL-6 protein secretion. In conclusion, IL-1α stimulates human CMF to express IL-1β, TNF-α, and IL-6 via specific signaling pathways, responses that are unaffected by IL-10 exposure.

The Impact of Royal Jelly against Hepatic Ischemia/Reperfusion-Induced Hepatocyte Damage in Rats: The Role of Cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF-α Signaling Pathways

2020 ◽  
Vol 14 (1) ◽  
pp. 88-100
Author(s):  
Fares E.M. Ali ◽  
Heba M. Saad Eldien ◽  
Nashwa A.M. Mostafa ◽  
Abdulrahman H. Almaeen ◽  
Mohamed R.A. Marzouk ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
P38 Mapk ◽  
Royal Jelly ◽  
Ischemia Reperfusion ◽  
Histopathological Changes ◽  
Down Regulation ◽  
Hepatic Ischemia ◽  
Tnf Α ◽  
Hepatic Ischemia Reperfusion ◽  
The Impact

Objective: The present study was conducted to elucidate the underlying molecular mechanism as well as the potential hepatoprotective effects of royal jelly (RJ) against hepatic ischemia/reperfusion (IR) injury. Methods: Rats were assigned into four groups; sham (received vehicle), IR (30 minutes ischemia and 45 minutes reperfusion), sham pretreated with RJ (200 mg/kg P.O.), and IR pretreated with RJ (200 mg/kg P.O.). The experiment has lasted for 28 days. Results: Hepatic IR significantly induced hepatic dysfunctions, as manifested by elevation of serum transaminases, ALP and LDH levels. Moreover, hepatic IR caused a significant up-regulation of P38-MAPK, NF-κB-p65, TNF-α and MDA levels along with marked down-regulation of Nrf-2, HO-1, COX-4, cytoglobin, IκBa, IL-10, GSH, GST and SOD levels. Additionally, marked histopathological changes were observed after hepatic IR injury. On the contrary, pretreatment with RJ significantly improved hepatic functions along with the alleviation of histopathological changes. Moreover, RJ restored oxidant/antioxidant balance as well as hepatic expressions of Nrf-2, HO-1, COX-4, and cytoglobin. Simultaneously, RJ significantly mitigated the inflammatory response by down-regulation of P38-MAPK, NF-κB-p65, TNF-α expression. Conclusion: The present results revealed that RJ has successfully protected the liver against hepatic IR injury through modulation of cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF-α signaling pathways.

scholarly journals Upregulation of Cytokines Is Detected in the Placentas of Cattle Infected with Neospora caninum and Is More Marked Early in Gestation When Fetal Death Is Observed

2008 ◽  
Vol 76 (6) ◽  
pp. 2352-2361 ◽  
Author(s):  
Anne Rosbottom ◽  
E. Helen Gibney ◽  
Catherine S. Guy ◽  
Anja Kipar ◽  
Robert F. Smith ◽  
...  
Keyword(s):  
Protein Expression ◽  
Fetal Death ◽  
Neospora Caninum ◽  
Late Gestation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Cytokine Mrna ◽  
Early Gestation ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT The protozoan parasite Neospora caninum causes fetal death after experimental infection of pregnant cattle in early gestation, but the fetus survives a similar infection in late gestation. An increase in Th1-type cytokines in the placenta in response to the presence of the parasite has been implicated as a contributory factor to fetal death due to immune-mediated pathological alterations. We measured, using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay, the levels of cytokines in the placentas of cattle experimentally infected with N. caninum in early and late gestation. After infection in early gestation, fetal death occurred, and the levels of mRNA of both Th1 and Th2 cytokines, including interleukin-2 (IL-2), gamma interferon (IFN-γ), IL-12p40, tumor necrosis factor alpha (TNF-α), IL-18, IL-10, and IL-4, were significantly (P < 0.01) increased by up to 1,000-fold. There was extensive placental necrosis and a corresponding infiltration of CD4+ T cells and macrophages. IFN-γ protein expression was also highly increased, and a modest increase in transforming growth factor β was detected. A much smaller increase in the same cytokines and IFN-γ protein expression, with minimal placental necrosis and inflammatory infiltration, occurred after N. caninum infection in late gestation when the fetuses survived. Comparison of cytokine mRNA levels in separated maternal and fetal placental tissue that showed maternal tissue was the major source of all cytokine mRNA except for IL-10 and TNF-α, which were similar in both maternal and fetal tissues. These results suggest that the magnitude of the cytokine response correlates with but is not necessarily the cause of fetal death and demonstrate that a polarized Th1 response was not evident in the placentas of N. caninum-infected cattle.

Abstract 393: Anti-inflammatory Properties of Aqueous Extracts of Sesame Oil

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Krithika Selvarajan ◽  
Chandrakala Aluganti Narasimhulu ◽  
Reena Bapputty ◽  
Sampath Parthasarathy
Keyword(s):  
Protein Expression ◽  
Aqueous Extract ◽  
Dietary Intervention ◽  
Sesame Oil ◽  
Luciferase Assay ◽  
Treatment Modalities ◽  
Raw 264.7 Cells ◽  
Mrna Levels ◽  
Tnf Α ◽  
Anti Inflammatory

Background Dietary intervention to prevent atherosclerosis and inflammation has been a major focus in recent years. Sesame oil (SO), widely used in many Asian countries, has been reported to help reduce high blood pressure. It has also been shown to reduce plasma cholesterol, low density lipoprotein (LDL) cholesterol and triglyceride levels. We previously reported that SO was effective in inhibiting atherosclerosis in LDL-receptor negative mice. In this study we tested whether the aqueous, non-lipid components of SO might have anti-inflammatory effects. Methods Sesame oil was extracted using ethanol:water mixture, lyophilized and reconstituted in water. To study anti-inflammatory effect, RAW 264.7 cells (macrophage cell line) were treated with the aqueous extract in the presence or absence of lipopolysaccharide (LPS) for 24 hours. RNA was extracted using Trizol. mRNA expression of inflammatory cytokines such as IL-1α, IL-6 and TNF-α were analyzed by real time PCR. Protein expression was determined by western blot analysis. To identify the mechanism of action, we performed luciferase assay using HepG2-LXR reporter cell lines. Results LPS induced the expression of IL-1α, IL-6 and TNF-α mRNA levels in RAW cells. The extract alone did not significantly affect the expressions of inflammatory cytokine genes. However, when treated together with LPS, sesame oil aqueous extract inhibited the mRNA levels of these cytokines significantly. Treatment with LPS together with SO extract also decreased the protein expression of these cytokines. The SO extract induced LXR expression as identified by the luciferase assay system in HepG2-LXR reporter cells. Conclusion These findings suggest that the aqueous portion of SO might be effective in preventing inflammation. Furthermore, the activation of LXR might suggest additional effects on lipid metabolism. Identifying the specific components present in the aqueous extract will be instrumental in developing treatment modalities for atherosclerosis and other inflammatory conditions.

scholarly journals Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

2018 ◽  
Vol 49 (2) ◽  
pp. 610-625 ◽  
Author(s):  
Chun-Yan He ◽  
Li-Peng Jiang ◽  
Cheng-Yue Wang ◽  
Yue Zhang
Keyword(s):  
Inflammatory Response ◽  
Protein Expression ◽  
Quantitative Polymerase Chain Reaction ◽  
Pyrrolidine Dithiocarbamate ◽  
Mrna Levels ◽  
Periodontal Ligament Fibroblasts ◽  
Necrosis Factor Alpha ◽  
Periodontal Tissues ◽  
Periodontal Inflammation ◽  
Tnf Α

Background/Aims: The roles of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in peri-implantitis are unclear. Here, we used a canine model of peri-implantitis to explore the effects of inhibiting NF-κB with pyrrolidine dithiocarbamate (PDTC) on the inflammatory response in ligature-induced peri-implantitis. Methods: After successfully establishing the peri-implantitis model, beagles were randomly assigned to normal, model or PDTC groups. ELISA tests were used to determine the levels of interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). Immunohistochemistry was employed to assess the expression of NF-κB p65. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the mRNA levels of TLR4 and NF-κB p65, and western blot analysis was used to measure the protein levels of TLR4 in periodontal tissues from each group. Periodontal ligament fibroblasts (PDLFs) were cultured and subsequently classified into PDLF normal, PDLF model, PDLF LPS, PDLF PDTC, and PDLF LPS + PDTC groups. An immunofluorescence assay was used to measure the expression level of NF-κB p65. The CCK-8 assay and flow cytometry were performed to evaluate cell proliferation and apoptosis. Results: The in vitro results indicated that NF-κB p65 and TLR4 were upregulated in canine periodontal tissues, and PDTC could suppress the expression levels of NF-κB p65 and TLR4. Inflammation could increase TLR4 protein expression in canine periodontal tissue, and PDTC could inhibit the inflammation-induced increase in TLR4 protein expression. These results revealed that PDTC could reverse the LPS-induced increases in the levels of IL-1, IL-6, IL-8 and TNF-α. In vivo, the results demonstrated that PDTC inhibited the LPS-induced NF-κB p65 upregulation, and PDTC could reverse the inhibitory effect of the PDLF model + LPS on the proliferation of periodontal fibroblasts. The results also showed that in the PDLF model, LPS promoted PDLF apoptosis by inducing implant periodontitis in canines, but PDTC inhibited the PDLF apoptosis and relieved implant periodontitis in canines. Conclusion: Based on our results, we concluded that PDTC can inhibit the expression of NF-κB and alleviate the inflammatory response induced by LPS, thereby preventing periodontal inflammation and reducing the development of peri-implantitis.

TLR5-mediated activation of p38 MAPK regulates epithelial IL-8 expression via posttranscriptional mechanism

2003 ◽  
Vol 285 (2) ◽  
pp. G282-G290 ◽  
Author(s):  
Yimin Yu ◽  
Hui Zeng ◽  
Sean Lyons ◽  
Adam Carlson ◽  
Didier Merlin ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Mrna Stability ◽  
Mrna Translation ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Maximal Inhibition ◽  
Mapk Activation ◽  
Intestinal Epithelia ◽  
Tnf Α ◽  
Sb 203580

Toll-like receptors (TLRs) activate antimicrobial gene expression in response to detection of specific bacterial products. Relatively little is known about TLR5, the only TLR thought to be preferentially expressed by epithelial cells, beyond that it confers activation of the transcription factor NF-κB in a MyD-88 dependent manner in response to flagellin. Because TLRs, in general, are also thought to signal through members of the MAPK family, we examined flagellin-induced MAPK activation (via examining its phosphorylation status) and its subsequent role in expression of the chemokine IL-8 in polarized intestinal epithelia. Flagellin, like other proinflammatory stimuli (TNF-α, Salmonella typhimurium), activated p38 MAPK in a TLR5-dependent manner, whereas aflagellate bacteria or EGF did not activate this kinase. Although ERK1 and -2 were also observed to be activated in response to flagellin, their activation was not restricted to proinflammatory stimuli because they were also potently activated by aflagellate bacteria ( S. typhimurium or Escherichia coli) and EGF (neither of which activate NF-κB in these cells). Pharmacological inhibition of p38 MAPK (by SB-203580) potently (IC50 = 10 nM) reduced expression of IL-8 protein (maximal inhibition, 75%) but had no effect on NF-κB activation, only slightly attenuated upregulation of IL-8 mRNA levels in response to flagellin, and did not effect IL-8 mRNA stability. Together, these results indicate that epithelial TLR5 mediates p38 activation and subsequently regulates flagellin-induced IL-8 expression independently of NF-κB, probably by influencing IL-8 mRNA translation.

scholarly journals High-Frequency Near-Infrared Diode Laser Irradiation Attenuates IL-1β-Induced Expression of Inflammatory Cytokines and Matrix Metalloproteinases in Human Primary Chondrocytes

2020 ◽  
Vol 9 (3) ◽  
pp. 881 ◽  
Author(s):  
Shuzo Sakata ◽  
Ryo Kunimatsu ◽  
Yuji Tsuka ◽  
Ayaka Nakatani ◽  
Tomoka Hiraki ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Protein Expression ◽  
Laser Irradiation ◽  
Diode Laser ◽  
High Frequency ◽  
Near Infrared ◽  
Mrna Levels ◽  
Induced Expression ◽  
Tnf Α

High-frequency near-infrared diode laser provides a high-peak output, low-heat accumulation, and efficient biostimulation. Although these characteristics are considered suitable for osteoarthritis (OA) treatment, the effect of high-frequency near-infrared diode laser irradiation in in vitro or in vivo OA models has not yet been reported. Therefore, we aimed to assess the biological effects of high-frequency near-infrared diode laser irradiation on IL-1β-induced chondrocyte inflammation in an in vitro OA model. Normal Human Articular Chondrocyte-Knee (NHAC-Kn) cells were stimulated with human recombinant IL-1β and irradiated with a high-frequency near-infrared diode laser (910 nm, 4 or 8 J/cm2). The mRNA and protein expression of relevant inflammation- and cartilage destruction-related proteins was analyzed. Interleukin (IL) -1β treatment significantly increased the mRNA levels of IL-1β, IL-6, tumor necrosis factor (TNF) -α, matrix metalloproteinases (MMP) -1, MMP-3, and MMP-13. High-frequency near-infrared diode laser irradiation significantly reduced the IL-1β-induced expression of IL-1β, IL-6, TNF-α, MMP-1, and MMP-3. Similarly, high-frequency near-infrared diode laser irradiation decreased the IL-1β-induced increase in protein expression and secreted levels of MMP-1 and MMP-3. These results highlight the therapeutic potential of high-frequency near-infrared diode laser irradiation in OA.

scholarly journals Protective Effect of the Abelmoschus manihot Flower Extract on DSS-Induced Ulcerative Colitis in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Bensheng Wu ◽  
Qing Zhou ◽  
Zongqi He ◽  
Xiaopeng Wang ◽  
Xueliang Sun ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Protein Expression ◽  
Therapeutic Effect ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Colon Tissue ◽  
Expression Levels ◽  
Caspase 1 ◽  
Tnf Α ◽  
Dose Dependent

Background. The flower of Abelmoschus manihot (AM) has been widely used in the treatment of chronic inflammatory diseases, including ulcerative colitis. This paper aimed to confirm the therapeutic effect of AM on ulcerative colitis (UC) and explore its mechanism. Methods. Mouse models were induced by 2.5% dextran sulfate sodium (DSS) and treated with AM. UC signs, symptoms, colon macroscopic lesion scores, and disease activity index (DAI) scores were observed. Colon levels of interleukin- (IL-) 6, IL-1β, IL-18, IL-17, tumor necrosis factor- (TNF-) α, and IL-10 were quantified by ELISA. The colon protein expression levels of NLRP3, ASC, caspase 1 p10, β-arrestin1, ZO-1, occludin-1, and claudin-1 were examined by immunohistochemistry and western blotting. The mRNA levels of IL-1β, IL-18, NLRP3, ASC, and caspase 1 p10 in the colon were determined by real-time quantitative polymerase chain reaction (qPCR). Results. After treatment with AM, the mortality of mice, pathological damage to the colon, splenomegaly, and the spleen coefficient were decreased. AM reduced the levels of proinflammatory cytokines (IL-6, IL-1β, IL-18, IL-17, and TNF-α) and increased the level of IL-10. The mRNA expression levels of NLRP3, ASC, and caspase 1 in colon tissue were decreased by AM in a dose-dependent manner. In addition, AM also reduced the protein expression of NLRP3, ASC, caspase 1 p10, IL-1β, IL-18, and β-arrestin1 in the colon tissue of model mice. Western blot analysis confirmed that AM increased the expression of occludin-1, claudin-1, and ZO-1 in a dose-dependent manner. Conclusion. This study shows that AM has a significant therapeutic effect on mice with UC, and the mechanism may be related to the inhibition of the β-arrestin1/NLRP3 inflammasome signaling pathway and the protection of intestinal barrier function.

scholarly journals Depletion of EREG Enhances the Osteo/Dentinogenic Differentiation Ability of Dental Pulp Stem Cells via P38 MAPK and Erk Pathway in Inflammatory Microenvironment

2021 ◽  
Author(s):  
Ran Ran ◽  
Haoqing Yang ◽  
Yangyang Cao ◽  
Wanhao Yan ◽  
Ying Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Erk Signaling ◽  
Mechanism Study ◽  
Differentiation Markers ◽  
Alizarin Red ◽  
Differentiation Potential ◽  
Tnf Α ◽  
Dentinogenic Differentiation

Abstract Background Epiregulin (EREG) is an important component of EGF, which was demonstrated to promote the osteo/dentinogenic differentiation of stem cells from SCAPs. Whether it could stimulate the osteo/dentinogenic differentiation of DPSCs in inflammatory environment is not clear. The purpose of the present study was to investigate the role of EREG on the DPSCs’ osteo/dentinogenic differentiation ability in inflammatory environment. Methods DPSCs were isolated from human third molars. Short hairpin RNAs (shRNAs) was used to knock down the EREG expression in DPSCs. Recombinant human EREG protein (rhEREG) was adopted in the rescue experiment. TNF-α was employed to mimic the inflammatory environment in vitro. Alkaline phosphatase (ALP) staining, Alizarin red staining, quantitative calcium analysis, and real time RT-PCR was used to detect the osteo/dentinogenic differentiation markers and related signaling pathways under normal and inflammatory environment. Results EREG depletion promoted ALP activity and mineralization ability of DPSCs. Expression of BSP, DMP-1, and DSPP were also enhanced. Besides, 50ng/ml rhEREG treatment weakened the osteo/dentinogenic differentiation potential. 10 ng/mL TNF-α treatment for 4h increased the expression of EREG in DPSCs. However, knockdown of EREG rescued the impaired osteo/dentinogenic differentiation ability caused by TNF-α treatment. Further mechanism study showed that, EREG depletion activated p38 MAPK and Erk signaling pathways in DPSCs under normal and inflammatory environment. Conclusions Our results demonstrated that EREG could inhibited the osteo/dentinogenic differentiation potential of DPSCs via p38 MAPK and Erk signaling pathways in normal and inflammatory environment.

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