scholarly journals Jieduquyuziyin Prescription-Treated Rat Serum Suppresses Activation of Peritoneal Macrophages in MRL/Lpr Lupus Mice by Inhibiting IRAK1 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Lina Ji ◽  
Xiaoli Hou ◽  
Xian Deng ◽  
Xuemin Fan ◽  
Aiwen Zhuang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Lupus Erythematosus ◽  
Peritoneal Macrophages ◽  
Rat Serum ◽  
Western Blot Method ◽  
Jieduquyuziyin Prescription ◽  
Chronic Autoimmune Disease ◽  
Cell Supernatant

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and Jieduquyuziyin prescription (JP) is a traditional Chinese medicine (TCM) formula that has been testified to be effective for SLE treatment as an approved hospital prescription for many years in China. However, its mechanism of action in the treatment of this disease is largely unknown. The purpose of this study was to determine whether JP-treated rat serum can inhibit the activation of peritoneal macrophages in MRL/lpr mice by downregulating the IRAK1 signaling pathway, thereby achieving the effect of improving SLE. The JP-treated rat serum was prepared, and the peritoneal macrophages of MRL/lpr lupus mice were isolated in vitro, and the effect of JP on cell viability was detected by the CCK8 method. After LPS induction and shRNA lentiviral transfection, the effect of JP on the expression of IRAK1 in cells was detected by immunofluorescence staining. The content of TNF-α and IL-6 in the cell supernatant was determined by ELISA. The expression of IRAK1, NF-κB, TNF-α, and IL-6 mRNA was detected by RT-PCR, and the expression levels of IRAK1, p-IRAK1, TRAF6, IKBα, p-IKBα, IKK + IKK, NF-κB, and p-NF-κB proteins was detected by western blot method. We investigated the role of JP in peritoneal macrophages of the MRL/lpr mouse and identified the possible mechanisms of action. The results showed that JP could reduce the phosphorylation of IRAK1 and its downstream proteins induced by LPS and inhibit the expression of inflammatory cytokines, including TNF-α and IL-6. In addition, after the transfection of cells with shRNA lentiviral, the results of JP tended to be consistent. In conclusion, JP may inhibit the activation of peritoneal macrophages in MRL/lpr mice by downregulating the IRAK1-NF-κB signaling pathway, and IRAK1 may be a potential target for JP treatment of SLE.

scholarly journals Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

scholarly journals Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 325 ◽  
Author(s):  
Xiaojuan Li ◽  
Yunping Tang ◽  
Fangmiao Yu ◽  
Yu Sun ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Nude Mouse Model ◽  
Dose Dependent

We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

scholarly journals Has-miR-875-5p Inhibits Tumorigenesis by Targeting USF2 via TGF-β Signaling Pathway in Gastric Cancer

2021 ◽  
Author(s):  
Shenshuo Gao ◽  
Zhikai Zhang ◽  
Xubin Wang ◽  
Yan Ma ◽  
Chensheng Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Research Direction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
New Research

Abstract Background: Gastric cancer (GC) is one of the most common malignancies, and more and more evdiences show that the pathogenesis is regulated by various miRNAs.In this study, we investigated the role of miR-875 in GC. Methods:The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA RT-PCR. The effect of miR-875-5p on GC proliferation was determined by CCK-8 proliferation assay and EDU assay. Migration and invasion were examined by transwell migration and invasion assay and wound healing assay. The interaction between miR-875-5p and its target gene USF2 was verified by a dual luciferase reporter assay. The effects of miR-875-5p in vivo were studied in xenograft nude mice models.Related proteins were detected by Western blot.Results:The results showed that miR-875-5p inhibited the proliferation, migration and invasion of gastric cancer cells in vitro, and inhibited tumorigenesis in vivo. USF2 proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracts the effects of miR-875-5p inhibitors.Overexpression of miR-875-5p can inhibit proliferation, migration, and invasion through the TGF-β signaling pathway by down-regulation of USF2 in GC, providing a new research direction for the diagnosis and targeted therapy of GC.Conclusions: MiR-875-5pcan inhibited the progression of GC by directly targeting USF2 and negatively regulating TGF-β signaling pathway.In the future, miR-875-5p is expected to be used as a potential therapeutic target for GC therapy.

scholarly journals YAP regulates porcine skin-derived stem cells self-renewal partly by repressing Wnt/β-catenin signaling pathway

2021 ◽  
Author(s):  
Hong-Chen Yan ◽  
Yu Sun ◽  
Ming-Yu Zhang ◽  
Shu-Er Zhang ◽  
Jia-Dong Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Adult Stem Cells ◽  
Self Renewal ◽  
Human Ascs ◽  
Regulation Mechanisms ◽  
Interfering Rna ◽  
Pluripotency Genes

Abstract Background Skin-derived stem cells (SDSCs) are a class of adult stem cells (ASCs) that have the ability to self-renew and differentiate. The regulation mechanisms involved in the differentiation of ASCs is a hot topic. Porcine models have close similarities to humans and porcine SDSCs (pSDSCs) offer an ideal in vitro model to investigate human ASCs. To date, studies concerning the role of yes-associated protein (YAP) in ASCs are limited, and the mechanism of its influence on self-renewal and differentiation of ASCs remain unclear. In this paper, we explore the link between the transcriptional regulator YAP and the fate of pSDSCs. Results We found that YAP promotes the pluripotent state of pSDSCs by maintaining the high expression of the pluripotency genes Sox2, Oct4. The overexpression of YAP prevented the differentiation of pSDSCs and the depletion of YAP by small interfering RNA (siRNAs) suppressed the self-renewal of pSDSCs. In addition, we found that YAP regulates the fate of pSDSCs through a mechanism related to the Wnt/β-catenin signaling pathway. When an activator of the Wnt/β-catenin signaling pathway, CHIR99021, was added to pSDSCs overexpressing YAP the ability of pSDSCs to differentiate was partially restored. Conversely, when XAV939 an inhibitor of Wnt/β-catenin signaling pathway, was added to YAP knockdown pSDSCs a higher self-renewal ability resulted. Conclusions our results suggested that, YAP and the Wnt/β-catenin signaling pathway interact to regulate the fate of pSDSCs.

scholarly journals A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

2009 ◽  
Vol 6 (5) ◽  
pp. 387-392 ◽  
Author(s):  
Yinan Wang ◽  
Xueling Cui ◽  
Guixiang Tai ◽  
Jingyan Ge ◽  
Nan Li ◽  
...  
Keyword(s):  
Critical Role ◽  
Peritoneal Macrophages ◽  
Activin A ◽  
Mouse Peritoneal Macrophages

scholarly journals IgE in the Pathogenesis of SLE: From Pathogenic Role to Therapeutic Target

Antibodies ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 69
Author(s):  
Yasmine Lamri ◽  
Nicolas Charles
Keyword(s):  
Lupus Erythematosus ◽  
Functional Outcomes ◽  
Allergic Diseases ◽  
Parasitic Infections ◽  
Pathogenic Role ◽  
Ige Antibodies ◽  
Therapeutic Modalities ◽  
Nuclear Antigens ◽  
Chronic Autoimmune Disease

Systemic lupus erythematosus (SLE) is a multifactorial chronic autoimmune disease, marked by the presence of autoantibodies to nuclear antigens belonging to different isotype classes. For several years, IgE antibodies have been incriminated in the development of allergic diseases and parasitic infections and different anti-IgE therapies have been developed to encounter the pathogenic role of IgE in these pathologies. Recently, multiple studies showed the presence of elevated total IgE levels and demonstrated a pathogenic role of autoreactive IgE in SLE. This review aims to summarize the findings incriminating IgE and autoreactive IgE in the pathophysiology of SLE, to describe their functional outcomes on their targeted cells as well as to discuss different IgE-related therapeutic modalities that emerged and that may be beneficial for SLE patient care.

Anti-angiogenic role of microRNA-23b in melanoma by disturbing NF-κB signaling pathway via targeted inhibition of NAMPT

2020 ◽  
Vol 16 (10) ◽  
pp. 541-458 ◽  
Author(s):  
Renrong Lv ◽  
Jing Yu ◽  
Qian Sun
Keyword(s):  
Signaling Pathway ◽  
Tumor Tissues ◽  
Melanoma Treatment ◽  
Melanoma Patients ◽  
Targeted Inhibition ◽  
Nicotinamide Phosphoribosyl Transferase ◽  
Poor Patient Survival

Aim: Melanoma is the major cause of death in patients inflicting skin cancer. We identify miR-23b plays an anti-angiogenic role in melanoma. Materials & methods: We collected tumor tissues from melanoma patients. Experiments in vivo and in vitro were designed to evaluate the role of miR-23b in melanoma. Results & conclusion: miR-23b was found to be downregulated in melanoma tissues, and associated with poor patient survival. Elevating miR-23b inhibited cell viability and colony formation, reduced pro-angiogenetic ability, and accelerated apoptosis in SK-MEL-28 cells. miR-23b targeted NAMPT. Disturbing NF-κB signaling pathway with ammonium pyrrolidinedithiocarbamate (an inhibitor of NF-kB signaling pathway) impeded acquired pro-angiogenetic ability of nicotinamide phosphoribosyl transferase-overexpressed SK-MEL-28 cells. MiR-23b is a prognostic factor in melanoma. This study provides an enhanced understanding of microRNA-based targets for melanoma treatment.

scholarly journals Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Hong-li Jiao ◽  
Bin-shu Weng ◽  
Shan-shan Yan ◽  
Zi-mo Lin ◽  
Shu-yang Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Ras Signaling ◽  
Invasion And Metastasis ◽  
In Vivo Models ◽  
Ras Signaling Pathway ◽  
Colorectal Cancer Progression

AbstractOxysterol-binding protein like protein 3 (OSBPL3) has been shown involving in the development of several human cancers. However, the relationship between OSBPL3 and colorectal cancer (CRC), particularly the role of OSBPL3 in the proliferation, invasion and metastasis of CRC remains unclear. In this study, we investigated the role of OSBPL3 in CRC and found that its expression was significantly higher in CRC tissues than that in normal tissues. In addition, high expression of OSBPL3 was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of OSBPL3 promoted the proliferation, invasion and metastasis of CRC in vitro and in vivo models. Moreover, we revealed that OSBPL3 promoted CRC progression through activation of RAS signaling pathway. Furthermore, we demonstrated that hypoxia induced factor 1 (HIF-1A) can regulate the expression of OSBPL3 via binding to the hypoxia response element (HRE) in the promoter of OSBPL3. In summary, Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway. This novel mechanism provides a comprehensive understanding of both OSBPL3 and the RAS signaling pathway in the progression of CRC and indicates that the HIF1A–OSBPL3–RAS axis is a potential target for early therapeutic intervention in CRC progression.

scholarly journals Hedgehog Inhibitors Suppress Osteoclastogenesis in In Vitro Cultures, and Deletion of Smo in Macrophage/Osteoclast Lineage Prevents Age-Related Bone Loss

2020 ◽  
Vol 21 (8) ◽  
pp. 2745
Author(s):  
Yukihiro Kohara ◽  
Ryuma Haraguchi ◽  
Riko Kitazawa ◽  
Yuuki Imai ◽  
Sohei Kitazawa
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Signaling Pathway ◽  
Early Stage ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Age Related ◽  
Hh Signaling

The functional role of the Hedgehog (Hh)-signaling pathway has been widely investigated in bone physiology/development. Previous studies have, however, focused primarily on Hh functions in bone formation, while its roles in bone resorption have not been fully elucidated. Here, we found that cyclopamine (smoothened (Smo) inhibitor), GANT-58 (GLI1 inhibitor), or GANT-61 (GLI1/2 inhibitor) significantly inhibited RANKL-induced osteoclast differentiation of bone marrow-derived macrophages. Although the inhibitory effects were exerted by cyclopamine or GANT-61 treatment during 0–48 h (early stage of osteoclast differentiation) or 48–96 h (late stage of osteoclast differentiation) after RANKL stimulation, GANT-58 suppressed osteoclast formation only during the early stage. These results suggest that the Smo-GLI1/2 axis mediates the whole process of osteoclastogenesis and that GLI1 activation is requisite only during early cellular events of osteoclastogenesis. Additionally, macrophage/osteoclast-specific deletion of Smo in mice was found to attenuate the aging phenotype characterized by trabecular low bone mass, suggesting that blockage of the Hh-signaling pathway in the osteoclast lineage plays a protective role against age-related bone loss. Our findings reveal a specific role of the Hh-signaling pathway in bone resorption and highlight that its inhibitors show potential as therapeutic agents that block osteoclast formation in the treatment of senile osteoporosis.

scholarly journals Role of β-Catenin Activation Levels and Fluctuations in Controlling Cell Fate

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 176 ◽  
Author(s):  
Elisa Pedone ◽  
Lucia Marucci
Keyword(s):  
Signaling Pathway ◽  
Cell Fate ◽  
Temporal Dynamics ◽  
Cellular Systems ◽  
Future Research ◽  
Somatic Cell Reprogramming ◽  
Development In Vitro ◽  
Pluripotency Maintenance

Cells have developed numerous adaptation mechanisms to external cues by controlling signaling-pathway activity, both qualitatively and quantitatively. The Wnt/β-catenin pathway is a highly conserved signaling pathway involved in many biological processes, including cell proliferation, differentiation, somatic cell reprogramming, development, and cancer. The activity of the Wnt/β-catenin pathway and the temporal dynamics of its effector β-catenin are tightly controlled by complex regulations. The latter encompass feedback loops within the pathway (e.g., a negative feedback loop involving Axin2, a β-catenin transcriptional target) and crosstalk interactions with other signaling pathways. Here, we provide a review shedding light on the coupling between Wnt/β-catenin activation levels and fluctuations across processes and cellular systems; in particular, we focus on development, in vitro pluripotency maintenance, and cancer. Possible mechanisms originating Wnt/β-catenin dynamic behaviors and consequently driving different cellular responses are also reviewed, and new avenues for future research are suggested.

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