scholarly journals The Novel Peptide AEDPPE Alleviates Trophoblast Cell Dysfunction Associated With Preeclampsia by Regulating the NF-κB Signaling Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Yixiao Wang ◽  
Yan Cao ◽  
Xiaohong Ji ◽  
Ting Li ◽  
Lu Xue ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Signaling Pathway ◽  
Rat Model ◽  
Biological Effects ◽  
Cytokine Expression ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
Tnf Α

Background: Preeclampsia (PE) is a serious risk to the health of pregnant women and fetuses during pregnancy, and there is no effective treatment for this condition. Although many reports have confirmed the therapeutic effects of peptides in diseases, the role of peptides in PE remains poorly understood.Methods: A differentially expressed peptide in PE (AEDPPE) is derived from heat-shock protein beta-1 (HSPB1), amino acids 100 to 109 (DVNHFAPDEL), which we identified in a previous study. We synthesized AEDPPE and investigated its effect on HTR-8/SVneo cell function using a Cell Counting Kit-8, flow cytometric assay, and Transwell and wound-healing assays. Quantitative reverse transcription-PCR and ELISA were used to determine cytokine expression. Pull-down assay, mass spectrometry, Western blot analysis, and immunofluorescence were used to explore the potential targets and signaling pathways regulated by AEDPPE. Finally, we assessed the effect of AEDPPE in the lipopolysaccharide (LPS)-induced PE-like rat model.Results: AEDPPE significantly promoted the migration and invasion of HTR-8/SVneo cells, and it decreased the expression of interleukins 1 beta (IL-1β), interleukin 6 (IL-6), and interleukin 8 (IL-8). These functions performed by AEDPPE remained evident after injury to HTR-8/SVneo cells with tumor necrosis factor-alpha (TNF-α), and AEDPPE reversed the elevated sFlt-1/PlGF ratio induced by TNF-α. AEDPPE may exert these biological effects by binding to heat-shock protein 90β (HSP 90β) and, thus, affect the NF-κB signaling pathway. In an LPS-induced PE-like rat model, AEDPPE significantly improved PE symptoms and fetal rat outcomes.Conclusion: Our study showed that AEDPPE enhanced trophoblast migration and invasion and reduced inflammatory cytokine expression, and we hypothesized that these actions involved the NF-κB signaling pathway. The use of AEDPPE may thus develop into a novel modality in the treatment of PE.

scholarly journals A Novel Spleen Tyrosine Kinase Inhibitor Suppresses Invasiveness of Rheumatoid Arthritis Fibroblast Like Synoviocytes and Improves Collagen Induced Arthritis

2020 ◽  
Author(s):  
Seon Uk Kim ◽  
Hyun Jung Yoo ◽  
Jung Ho Kim ◽  
Hae Jun Hwang ◽  
Jin Kyun Park ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
Spleen Tyrosine Kinase ◽  
Collagen Induced Arthritis ◽  
Tnf Α ◽  
Clinical Arthritis ◽  
Syk Inhibitor ◽  
Fibroblast Like Synoviocytes

Abstract Background/PurposeRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by bone and cartilage destruction with leukocyte infiltration and activation at synovial tissue. The fibroblast-like synoviocytes (FLS) have a central role in disease pathogenesis and their invasiveness correlates with articular damage in RA patients. Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase known to have a crucial role in immune receptor signaling. This study aimed to evaluate the inhibitory effect of a novel small-molecule SYK inhibitor, SKI-O-592, on the invasiveness of RA FLS and inflammation of monocytes in vitro and in a mouse collagen-induced arthritis (CIA) model in vivo.MethodsFLS were isolated from synovial tissues of RA patients. FLS were treated with SKI-O-592 for 1 hr and then stimulated with tumor necrosis factor-alpha (TNF-α) for 48 hr. After stimulation, cell viability was measured using cell counting kit-8 (CCK-8) assay. The levels of IL-6, IL-8, CXCL10, MMP-3, and TNF-α were measured in culture supernatant of RA FLS and the monocytic cell line THP-1 cells by ELISA. Wound healing assay transwell migration and invasion assay using RA FLS was performed to evaluate cell migration ability. The adhesion ability of FLS was evaluated by co-culture with calcein-AM labeled THP-1 cells, and the expression of VCAM-1, ICAM-1, α-tubulin, β-actin, total and phosphorylated SYK, c-Jun N-terminal kinase (JNK), p38, ERK, phosphorylated c-Jun, mitogen-activated protein kinase kinase 4 (MKK4), and MKK3/6 was determined by Western blotting. CIA was developed in DBA/1J mice. Clinical arthritis score and histological scores were evaluated after treatment with SKI-O-592.ResultsSKI-O-592 reduced the secretion of chemokine, CXCL10 in RA FLS. Migration of cells to the wound region and through membrane pores and matrigel were decreased by SKI-O-592. Phosphorylation of JNK and p38 was reduced by SKI-O-592 after TNF-α stimulation. SKI-O-592 decreased secretion of TNF-α levels dose-dependently in THP-1 cells with IgG stimulation. The viability and proliferation of FLS and THP-1 were not affected by SKI-O-592. In the CIA model, scores for clinical arthritis and histology were decreased following SKI-O-592 treatment.ConclusionSKI-O-592 inhibited the invasiveness of RA FLS and had an anti-inflammatory effect on monocytes. SKI-O-592 exhibited therapeutic effects in the mouse CIA model by improving clinical and histological scores with amelioration of joint destruction. In conclusion, a novel SYK inhibitor, SKI-O-592, may provide a new therapeutic option for RA patients.

scholarly journals Stress-induced activation of ovarian heat shock protein 90 in a rat model of polycystic ovary syndrome

2011 ◽  
Vol 38 (2) ◽  
pp. 396-407 ◽  
Author(s):  
Eunkuk Park ◽  
John F. Cockrem ◽  
Kyung-Hoon Han ◽  
Doh-Hee Kim ◽  
Min-Hyung Jung ◽  
...  
Keyword(s):  
Heat Shock ◽  
Polycystic Ovary Syndrome ◽  
Heat Shock Protein ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Heat Shock Protein 90 ◽  
Ovary Syndrome

Germ cell-specific heat shock protein 70-2 is expressed in cervical carcinoma and is involved in the growth, migration, and invasion of cervical cells

Cancer ◽  
2010 ◽  
Vol 116 (16) ◽  
pp. 3785-3796 ◽  
Author(s):  
Manoj Garg ◽  
Deepika Kanojia ◽  
Shikha Saini ◽  
Sushma Suri ◽  
Anju Gupta ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Germ Cell ◽  
Specific Heat ◽  
Cervical Carcinoma ◽  
Heat Shock Protein 70 ◽  
Migration And Invasion ◽  
Cervical Cells

scholarly journals Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiye Chen ◽  
Yongjian Zhang ◽  
Yongcheng Wang ◽  
Ping Jiang ◽  
Guofeng Zhou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Experimental Studies ◽  
Matrix Metalloproteinase 2 ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Active Ingredients ◽  
Active Compounds ◽  
Guizhi Decoction

Abstract Background Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. Methods The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. Results A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C–C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1β, MMP-2 and MMP-9 in rats. Conclusion The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

scholarly journals PI3K/AKT Signaling Pathway Mediates the Proliferation, Migration and Invasion of Papillary Craniopharyngioma Cells

2020 ◽  
Author(s):  
Lin Zhou ◽  
Cheng Xing Yang ◽  
Lin Chun Fang ◽  
You Yuan Bao ◽  
Zhi Gang Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Specific Cell ◽  
Primary Cells ◽  
Akt Signaling Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Growth And Survival ◽  
Pi3k Signaling Pathway

Abstract Objective:Craniopharyngiomas are rare, histologically benign but clinically challenging neoplasms. Here, we aimed to interrogate the effect and significance of Phosphatidylinositol-3-kinase (PI3K) signaling pathway on papillary craniopharyngioma (PCP) cell growth and survival.Methods: We used Western blotting (WB) experiments to evaluate the expression of the PI3K/protein kinase B (AKT) in Craniopharyngiomas tissues, relative to health tissues. Primary tumor cells were obtained from fresh PCP samples by cell culture and then determined by cell morphology, immunofluorescence staining and expression of specific cell markers. In this study, PCP cell lines, isolated from fresh PCP samples, were treated with different concentrations of LY294002, a PI3K/AKT signaling inhibitor, to evaluate their proliferation, migration and invasion. We determined the cell proliferation using Cell Counting Kit-8 and colony formation. We then used flow cytometry to evaluate cell apoptosis and cell cycle. In addition, cell migration and invasion levels were determined by wound healing and Transwell assays, respectively.Results: Our data demonstrated that the expression of phosphorylated-PI3K/AKT was upregulated in human craniopharyngioma tissues compared to the normal control tissues. Immunofluorescence assays showed the presence of cytokeratin (pan CK) and vimentin protein (VIM) in the PCP primary cells. Furthermore, inhibition of PI3K/AKT signaling blocks the proliferation, migration and invasion of the PCP primary cells.Conclusions:Taken together, our data robustly demonstrates that the PI3K/AKT signaling pathway mediates the proliferation, migration and invasion of the PCP cells.

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