scholarly journals T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shan Cong ◽  
Yan Meng ◽  
Lingrui Wang ◽  
Jiao Sun ◽  
Ta bu shi·Nu er xia ti ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Protein Expression ◽  
Knee Osteoarthritis ◽  
Signaling Pathway ◽  
Underlying Mechanism ◽  
Cartilage Tissue ◽  
Inflammatory Factors ◽  
Dependent Manner ◽  
Tnf Α ◽  
Mrna And Protein Expression

Abstract Background The aim of this study was to investigate the effect of Iguratimod (T-614) on rat knee osteoarthritis (KOA) and further to explore its underlying mechanism. Methods In this study, papain-induced KOA model was constructed. Hematoxylin and eosin (H&E) staining was conducted to observe the pathological changes of cartilage tissue and Mankin scoring principle was used for quantitative scoring. Transmission electron microscopy (TEM) was applied to observe the ultrastructure of cartilage tissue. ELISA was used to measure the levels of matrix metalloproteinase 13 (MMP-13) and inflammatory factors (interleukin (IL)-6 and tumor necrosis factor a (TNF-a)) in serum. RT-qPCR and immunohistochemistry were conducted to detect mRNA expression and protein expression of key genes in Wnt/β-catenin pathway. Results H&E, Mankin scoring, and TEM data confirmed that compared with model group, T-614 significantly improved the degeneration of articular cartilage. Besides, we observed that low, middle, and high doses of T-614 could decrease the levels of MMP13, TNF-α, and IL-6 in serum to different degrees. Mechanically, T-614 downregulated the mRNA and protein expression of β-catenin and MMP13 in cartilage tissue via a dose-dependent manner, and on the contrary upregulated the mRNA and protein expression of glucogen synthase kinase-3 beta (GSK-3β). Conclusion Our results suggested that T-614 can reduce the level of its downstream target gene MMP-13 and downregulate the expression of inflammatory cytokines TNF-α and IL-6 by regulating the Wnt/β-catenin signaling pathway, thereby inhibiting joint inflammation and controlling KOA degeneration of articular cartilage.

scholarly journals LIPUS inhibits inflammation and catabolism through the NF‐κB pathway in human degenerative nucleus pulposus cells

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Weiwei Yi ◽  
Qing Chen ◽  
Chuan Liu ◽  
Kaiting Li ◽  
Bailong Tao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Real Time ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Real Time Pcr ◽  
Inflammatory Factors ◽  
Nucleus Pulposus Cells ◽  
Tnf Α ◽  
Gene And Protein Expression ◽  
Collagen Ii

Abstract Background Low-intensity pulsed ultrasound (LIPUS) is a safe and noninvasive rehabilitative physical therapy with anti-inflammatory effects. The current study investigated the effect of LIPUS on the inflammation of nucleus pulposus (NP) cells and its underlying mechanism. Methods Human NP cells were acquired from lumbar disc herniation tissue samples and cultured for experiments. Human NP cells were treated with LPS and then exposed to LIPUS (15 mW/cm2, 30 mW/cm2 and 60 mW/cm2) for 20 min daily for 3 days to determine the appropriate intensity to inhibit the expression of the inflammatory factors TNF-α and IL-1β. The gene and protein expression of aggrecan, collagen II, MMP-3 and MMP-9 was measured by real‐time PCR and western blotting, respectively. The activity of the nuclear factor‐kappa B (NF‐κB) pathway was examined by western blotting and immunofluorescence. After pretreatment with the NF-κB inhibitor PDTC, the expression of TNF-α, IL-1β, MMP-3 and MMP-9 was measured by real‐time PCR. Results LIPUS at intensities of 15 mW/cm2, 30 mW/cm2 and 60 mW/cm2 inhibited LPS-induced NP cell expression of the inflammatory factors TNF-α and IL-1β, especially at 30 mW/cm2. LIPUS significantly upregulated the gene and protein expression of aggrecan and collagen II and downregulated the gene and protein expression of MMP-3 and MMP-9 in LPS-induced NP cells. The NF‐κB signaling pathway was inhibited by LIPUS through inhibiting the protein expression of p-P65 and the translocation of P65 into the nucleus in LPS-induced NP cells. In addition, LIPUS had similar effects as the NF-κB inhibitor PDTC by inhibiting the NF-κB signaling pathway, inflammation and catabolism in LPS-induced human degenerative nucleus pulposus cells. Conclusion LIPUS inhibited inflammation and catabolism through the NF‐κB pathway in human degenerative nucleus pulposus cells.

scholarly journals Icariin induces autophagy and apoptosis of chondrocytes by inhibiting NF-κB signaling pathway

2020 ◽  
Vol 19 (9) ◽  
pp. 1851-1856
Author(s):  
Jun Xiong ◽  
Hui Zou ◽  
Yi Yu
Keyword(s):  
Polymerase Chain Reaction ◽  
Signaling Pathway ◽  
The Other ◽  
Cartilage Tissue ◽  
Inflammatory Factors ◽  
Chain Reaction ◽  
Tnf Α ◽  
Protein Expressions ◽  
Cartilage Cells ◽  
Polymerase Chain

Purpose: To investigate the effect of icariin on autophagy and apoptosis of chondrocytes, and the associated mechanisms.Methods: The chondrocytes were randomly divided into control (PBS intervention), TNF-α intervention, icarin +TNF-α, and NF-κB inhibition +TNF-α, with 8 strains in each group. The levels of IL-1, IL-6 and IL-12 were assayed by ELISA. The mRNA and protein expressions of ATG5, ATG7, Bax and Bcl-2 cells were determined by polymerase chain reaction (PCR) and Western blotting, while protein expressions of p-p65 and IκBα were assayed using Western blotting.Results: In the cartilage tissue of rats in the icariin +TNF-α group and NF-κB inhibition +TNF-α group, IL-1, IL-6 and IL-12 levels were significantly lower than those in TNF-α treatment group (p < 0.05). The AATG5 mRNA and protein in cartilage tissues of rats in icariin +TNF-α and NF-κB inhibition +TNF-α groups were significantly higher than those in TNF-α group. Bax mRNA and protein in cartilage tissues of icariin +TNF-α and NF-κB inhibition +TNF-α groups were downregulated, relative to TNF-α group; on the other hand, Bcl-2 mRNA and protein were significantly higher than those of TNF-α group (p < 0.05). In the cartilage tissues of Icarin +TNF-α, NF-κB inhibition +TNF-α groups, P-p65 protein was significantly lower than that of TNF-α (p < 0.05).Conclusion: TNF-α enhances the production of a large number of inflammatory factors by cartilage cells, inhibits autophagy of cartilage cells, and promotes cell apoptosis through regulation of NF-κB signaling pathway. Keywords: Icariin, NF-κB signaling pathway, TNF-α, Inflammatory response, Chondrocytes, Autophagy, Apoptosis

Simvastatin Improve ADAMTS13 mRNA and Protein Expression in Podocytes.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2246-2246
Author(s):  
Lei Shen ◽  
Guoyuan Lu ◽  
Ningzheng Dong ◽  
Zhenni Ma ◽  
Changgeng Ruan
Keyword(s):  
Protein Expression ◽  
Conflicts Of Interest ◽  
Inflammatory Factors ◽  
Dependent Manner ◽  
Independent Manner ◽  
Protein Levels ◽  
Severe Deficiency ◽  
Mrna And Protein Expression ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Abstract 2246 Aim: ADAMTS13 is a specific VWF (von Willebrand factor) -cleaving protease, which severe deficiency is the main cause of thrombotic thrombocytopenic purpura. ADAMTS13 is mainly synthesized and released of the surface of hepatic stellate cells and endothelial cells, but is alsoexpressed in other cells, including kidneypodocytes. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, not only has benefit action on atherosclerosis but also has anti-inflammatory and antithrombotic properties. Recent study indicated that ADAMTS13 can reduce inflammatory plaque formation during early atherosclerosis in mice. In this study, we investigate the effects of simvastatinon inflammatory factors-induced ADAMTS13 expression in podocytes. Methods: A conditionally immortalized mouse podocyte cell line was used in the study. Inflammatory factors (TNF-Á, IL-4, IL-6) and simvastatin were added to cell culture medium to exam their effect on ADAMTS13expresion in podocytes. We examedADAMTS13mRNA and protein expressbyquantitative real-time PCR (qRT-PCR) and Western blotting. Results: Our results showed that ADAMTS13 mRNA and protein was expressed in podocytes, and its expression levels were significantly decreased in cells treated withdifferent concentrations of IL-4 (1, 5,10 ng/mL) and IL-6(1,10, 100 ng/mL), while TNF-Á almost had no effect on ADAMTS13 expression. When podocytes treated with simvastatin (1 and 10 Ìmol/L), ADAMTS13 mRNA were significantly increased (1.53 ± 0.80 and 3.46 ±1.70, respectively, p<0.01 vs control), and ADAMTS13 protein levels were also increased (2.05 ± 0.18 and 2.22±0.12, respectively, p<0.01 vs control). Simvastatin also can reverse the inhibition effect of IL-6 (100 ng/mL) and IL-4 (10 ng/mL) on ADAMTS13 mRNA and protein expression in podocytes in a dose-independent manner. Conclusions: We demonstrate that different inflammatory cytokines had different influence on ADAMTS13's expression in podocytes. Simvastatin can increase the expression of ADAMTS13 in a dose-dependent manner with or without IL-6 and IL-4, which may be a very relevant compartment for the antithrombotic property of simvastatin. Disclosures: No relevant conflicts of interest to declare.

scholarly journals IL-33-Induced Transcriptional Activation of LPIN1 Accelerates Breast Tumorigenesis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2174
Author(s):  
Jin-Young Kim ◽  
Garam Kim ◽  
Sung-Chul Lim ◽  
Hong-Seok Choi
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Transcriptional Activation ◽  
Breast Cancer Cells ◽  
Regulatory Mechanism ◽  
Mammary Tumorigenesis ◽  
Underlying Mechanism ◽  
Breast Tumorigenesis ◽  
Mrna And Protein Expression ◽  
First Time

Phospholipids are crucial materials that are not only required for cell membrane construction but also play significant roles as signaling molecules. LPIN1 is an enzyme that displays phosphatidate phosphatase activity in the triglyceride and phospholipid synthesis pathway. Recent studies have shown that overexpression of LPIN1 is involved in breast tumorigenesis, but the underlying mechanism regulating LPIN1 expression has not been elucidated yet. In the present study, we showed that the IL-33-induced COT-JNK1/2 signaling pathway regulates LPIN1 mRNA and protein expression by recruiting c-Jun to the LPIN1 promoter in breast cancer cells. IL-33 dose-dependently and time-dependently increased LPIN1 mRNA and protein expression. Moreover, IL-33 promoted colony formation and mammary tumorigenesis via induction of LPIN1 expression, while inhibition of LPIN1 disturbed IL-33-induced cell proliferation and mammary tumorigenesis. IL-33-driven LPIN1 expression was mediated by the COT-JNK1/2 signaling pathway, and inhibition of COT or JNK1/2 reduced LPIN1 expression. COT-JNK1/2-mediated IL-33 signaling activated c-Jun and promoted its binding to the promoter region of LPIN1 to induce LPIN1 expression. These findings demonstrated the regulatory mechanism of LPIN1 transcription by the IL-33-induced COT/JNK1/2 pathway for the first time, providing a potential mechanism underlying the upregulation of LPIN1 in cancer.

scholarly journals Oral Administration of Salmon Cartilage Proteoglycan Attenuates Osteoarthritis in a Monosodium Iodoacetate-Induced Rat Model

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2098211
Author(s):  
Tuyen Danh Le ◽  
Hien Thi Thu Vu ◽  
Iddamalgoda Arunasiri ◽  
Kenichi Ito ◽  
Tadahiro Makise ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Knee Osteoarthritis ◽  
Rat Model ◽  
Interleukin 1Β ◽  
Cartilage Tissue ◽  
Necrosis Factor Alpha ◽  
Nasal Cartilage ◽  
Tnf Α ◽  
Monosodium Iodoacetate

Proteoglycan (PG) is a type of glycoprotein which forms an extracellular matrix with collagen and hyaluronic acid to maintain articular cartilage, synovial membrane, and synovial fluid. This study aimed to evaluate the antiosteoarthritis effects of salmon nasal cartilage-derived PG in alleviating knee osteoarthritis in an osteoarthritis rat model. Knee osteoarthritis was induced in rats by intra-articular injection of monosodium iodoacetate (MIA), 3 mg/knee, to the right knee. Animals were then administered either diclofenac (3 mg/kg body weight [b.w]/day) or proteoglycan F (PGF; 40 mg/kg and 120 mg/kg b.w/day) by oral gavage for 6 consecutive weeks. Knee diameters were measured throughout the experimental period; serum interleukin-1β and tumor necrosis factor-alpha (TNF-α) levels, and histological analysis of the ligament were carried out at the end of the experiment. Salmon cartilage PG considerably alleviated the osteoarthritis symptoms in the model and lowered the serum concentrations of interleukin-1β and TNF-α. Diclofenac 3 mg/kg/day and PGF at doses of 40 mg/kg/day and 120 mg/kg/day also improved articular cartilage structure on further histological studies. This study demonstrated the in vivo effect of salmon cartilage PG in attenuating symptoms in an MIA-induced rat model, including reduction of inflammatory markers and histological improvement of cartilage tissue.

scholarly journals Effect of TNF-α Inhibition on Bone Marrow-Derived Mesenchymal Stem Cells in Neurological Function Recovery after Spinal Cord Injury via the Wnt Signaling Pathway in a Rat Model

2017 ◽  
Vol 42 (2) ◽  
pp. 743-752 ◽  
Author(s):  
Ren-Jun Peng ◽  
Bing Jiang ◽  
Xi-Ping Ding ◽  
He Huang ◽  
Yi-Wei Liao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Rat Model ◽  
Wnt Signaling Pathway ◽  
Control Group ◽  
Tnf Α ◽  
Cord Injury ◽  
Mrna And Protein Expression ◽  
Gsk 3Β

Aim: The present study aimed to examine the effect of tumor necrosis factor-α (TNF-α) inhibition on bone marrow-derived mesenchymal stem cells (BMSCs) in neurological function recovery after spinal cord injury (SCI) via the Wnt signaling pathway in a rat model. Methods: The rat model of SCI was established using Allen’s method. Seventy-two adult male Sprague Dawley (SD) rats were randomly assigned into 4 groups (18 rats in each group): the sham control group, saline control group, BMSCs group (injection with BMSCs at the injured site) and BMSCs + TNF-α group (injection with BMSCs under TNF-α treatment at the injured site). Immunochemistry was performed to characterize the culture media after TNF-α-induced differentiation. qRT-PCR and Western blotting analyses were performed to detect the mRNA and protein expression of β-catenin, Wnt3a, GSK-3β and Axin. The Basso Beattie Bresnahan (BBB) locomotor score, neurological deficit score (NDS), and balance beam test (BBT) score were used to assess neurological functional recovery of SCI rats. Results: In the BMSC group, numerous spherical cell clusters grew in suspension, and the cells were nestin-, NF200- and GFAP-positive. Compared with the sham control and BMSC groups, the β-catenin and Wnt3a mRNA and protein expression was increased, but the GSK-3β and Axin mRNA and protein expression was decreased in the BMSCs + TNF-α group. The SCI rats in the BMSCs + TNF-α group exhibited lower BBB scores, and higher NDSs and BBT scores compared to the BMSCs group. Conclusion: Our study provides evidence that TNF-α inhibition may weaken the ability of BMSCs in neurological functional recovery after SCI by activating the Wnt signaling pathway.

Gabapentin Reduces Alcohol Intake in Rats by Regulating NF-κB Signaling Pathway Via PPAR γ

2021 ◽  
Author(s):  
Jing Li ◽  
Kewei Xu ◽  
Hao Ding ◽  
Qiaozhen Xi
Keyword(s):  
Locomotor Activity ◽  
Signaling Pathway ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Ethanol Consumption ◽  
Diglycidyl Ether ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Tnf Α

Abstract Aims Increasing preclinical and clinical reports have demonstrated the efficacy of gabapentin (GBP) in treating alcohol use disorder (AUD). However, the mechanism of the effects of GBP in AUD is largely unknown. Herein, we sought to investigate the effect of GBP in a rat model of AUD and explore the underlying mechanism. Methods The intermittent access to 20% ethanol in a 2-bottle choice (IA2BC) procedure was exploited to induce high voluntary ethanol consumption in rats. The rats were treated daily for 20 days with different doses of GBP, simultaneously recording ethanol/water intake. The locomotor activity and grooming behavior of rats were also tested to evaluate the potential effects of GBP on confounding motor in rats. The levels of IL-1β and TNF-α in serum and hippocampus homogenate from the rats were detected by using ELISA. The expressions of peroxisome proliferator-activated-receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) in the hippocampus were determined by immunofluorescence and western blot. Results GBP reduced alcohol consumption, whereas increased water consumption and locomotor activity of rats. GBP was also able to decrease the levels of IL-1β and TNF-α in both serum and hippocampus, in addition to the expression of NF-κB in the hippocampus. Furthermore, these effects attributed to GBP were observed to disappear in the presence of bisphenol A diglycidyl ether (BADGE), a specific inhibitor of PPAR-γ. Conclusions Our findings revealed that GBP could activate PPAR-γ to suppress the NF-κB signaling pathway, contributing to the decrease of ethanol consumption and ethanol-induced neuroimmune responses.

scholarly journals Methylprednisolone Protects SAP and Pancreatitis-Associated ALI in Mice by Inhibiting NLRP3 Inflammasome Through NF-κB

2020 ◽  
Author(s):  
Chuan-jiang Liu ◽  
Qiang Fu ◽  
Wenjing Zhou ◽  
Xu Zhang ◽  
Rui Chen ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Nlrp3 Inflammasome ◽  
Antioxidant Properties ◽  
Underlying Mechanism ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Expression Levels ◽  
Tnf Α

Abstract Background: Methylprednisolone (MP) is a synthetic corticosteroid with potent anti-inflammatory and antioxidant properties used as therapy for a variety of diseases. The underlying mechanism of MP to reduce acute pancreatitis still needs to be elucidated.Methods: Twenty-four male C57BL/6 mice (6-8 weeks) were used to establish SAP mouse model by administering an intraperitoneal injection of Cae and LPS. Amylase expression levels of serum and PLF were measured with an amylase assay kit. The concentrations of IL-1β and TNF-α in the serum and PLF were detected by ELISA. The level of pancreatic and lung tissue damage and inflammation was assessed by H&E staining and immunofluorescence staining. Western blot and qPCR were used to detect the expression levels of NLRP3, IL-1β and TNF-αin vivo and in vitro.Results: In this study, we found MP, used in the early phase of SAP, decreased the levels of IL-1β and TNF-α in serum and peritoneal lavage fluids (PLF), reduced the level of serum amylase and the expression of MPO in lung tissue, attenuated the pathological injury of the pancreas and lungs in a dose-dependent manner. The expression of NLRP3 and IL-1β in pancreas and lungs was down-regulated significantly depending on the MP concentration. In vitro, MP reduced the levels of IL-1β and TNF-α by down-regulating the expression of NLRP3, IL-1β and p-NF-κB in isolated peritoneal macrophages. Conclusion: MP can attenuate the injury of pancreas and lungs, and the inflammatory response in SAP mice by down-regulating the activation of NF-κB and the NLRP3 inflammasome.

scholarly journals CACNA1B (Cav2.2) Overexpression and Its Association with Clinicopathologic Characteristics and Unfavorable Prognosis in Non-Small Cell Lung Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoyu Zhou ◽  
Wei Wang ◽  
Shu Zhang ◽  
Xudong Wang ◽  
Zhiyuan Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Underlying Mechanism ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinicopathologic Characteristics ◽  
Incidence And Mortality ◽  
Mrna And Protein Expression

CACNA1B (Cav2.2) encodes an N-type voltage-gated calcium channel (VGCC) ubiquitously expressed in brain and peripheral nervous system that is important for regulating neuropathic pain. Because intracellular calcium concentration is a key player in cell proliferation and apoptosis, VGCCs are implicated in tumorigenesis. Recent studies have identified CACNA1B (Cav2.2) being overexpressed in prostate and breast cancer tissues when compared to adjacent normal tissues; however, its role in non-small cell lung cancer (NSCLC) has not been investigated. In this study, we determined the mRNA and protein expression of CACNA1B (Cav2.2) in NSCLC tumorous and adjacent nontumorous tissues by quantitative reverse transcription PCR (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC), respectively. CACNA1B (Cav2.2) protein expressions in tumorous tissues were correlated with NSCLC patients’ clinical characteristics and overall survival. CACNA1B (Cav2.2) mRNA and protein expression levels were higher in NSCLC tumorous tissues than in nontumorous tissues. High CACNA1B (Cav2.2) protein expression was associated with higher TNM stages, and CACNA1B (Cav2.2) protein expression is an independent prognostic marker in NSCLC. Based on our results, we conclude that CACNA1B (Cav2.2) plays a role in NSCLC development and progression. Elucidating the underlying mechanism may help design novel treatment by specifically targeting the calcium regulation pathway for NSCLC, a devastating disease with increasing incidence and mortality in China.

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