scholarly journals MiR-9-5p promotes MSC migration by activating β-catenin signaling pathway

2017 ◽  
Vol 313 (1) ◽  
pp. C80-C93 ◽  
Author(s):  
Xianyang Li ◽  
Lihong He ◽  
Qing Yue ◽  
Junhou Lu ◽  
Naixin Kang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Focal Adhesions ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Migration Ability ◽  
Tissue Damages ◽  
First Time ◽  
Hepatocyte Growth ◽  
High Migration

Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages, but the very limited number of cells that migrate to the damaged region strongly restricts their therapeutic applications. Full understanding of mechanisms regulating MSC migration will help to improve their migration ability and therapeutic effects. Increasing evidence shows that microRNAs play important roles in the regulation of MSC migration. In the present study, we reported that miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs with high migration ability. Overexpression of miR-9-5p promoted MSC migration, whereas inhibition of endogenous miR-9-5p decreased MSC migration. To elucidate the underlying mechanism, we screened the target genes of miR-9-5p and report for the first time that CK1α and GSK3β, two inhibitors of β-catenin signaling pathway, were direct targets of miR-9-5p in MSCs and that overexpression of miR-9-5p upregulated β-catenin signaling pathway. In line with these data, inhibition of β-catenin signaling pathway by FH535 decreased the miR-9-5p-promoted migration of MSCs, while activation of β-catenin signaling pathway by LiCl rescued the impaired migration of MSCs triggered by miR-9-5p inhibitor. Furthermore, the formation and distribution of focal adhesions as well as the reorganization of F-actin were affected by the expression of miR-9-5p. Collectively, these results demonstrate that miR-9-5p promotes MSC migration by upregulating β-catenin signaling pathway, shedding light on the optimization of MSCs for cell replacement therapy through manipulating the expression level of miR-9-5p.

scholarly journals Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

2018 ◽  
Vol 237 (2) ◽  
pp. 123-137 ◽  
Author(s):  
Min Hu ◽  
Yuehui Zhang ◽  
Jiaxing Feng ◽  
Xue Xu ◽  
Jiao Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Polycystic Ovary ◽  
Metformin Therapy ◽  
Before And After ◽  
Elevated Expression ◽  
Targeted Gene Expression ◽  
First Time

Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here, we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions.

scholarly journals Traditional Uyghur medicine Quercus infectoria galls water extract triggers apoptosis and autophagic cell death in colorectal cancer cells

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hui Zhang ◽  
Yongbing Wang ◽  
Jiayang Liu ◽  
Kudelaidi Kuerban ◽  
Jian Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Flow Cytometry ◽  
Cell Death ◽  
Alternative Medicine ◽  
Signaling Pathway ◽  
Water Extract ◽  
Underlying Mechanism ◽  
Autophagic Cell Death ◽  
Therapeutic Effects ◽  
Traditional Uyghur Medicine

Abstract Background The water extract of Quercuse infectoria galls (QIG) is the active ingredient of Uyghur medicine Xipayi Kui Jie’an (KJA) which has promising therapeutic effects on Ulcerative Colitis (UC) as an alternative medicine. Considering the relationship between UC and the development of colorectal cancer (CRC), the present work aims to explore the direct anti-CRC activity of QIG extract. Methods CCK8 assay and flow cytometry were used to detect cytotoxicity and apoptosis. Transmission electron microscopy (TEM), flow cytometry, laser confocal and western blotting were performed to examine autophagy. We also adopted Reactive Oxygen Assay kit, as well as transwell and wound healing tests to study the underlying mechanism of QIG against CRC cells. Results First, we found that QIG extract could suppress the viability of CRC cells and trigger caspases-dependent apoptosis. Subsequently, we proved for the first time that QIG extract also triggered autophagic cell death in CRC cells, which together with apoptosis contributed to the cytotoxic effect on CRC cells. Further investigation revealed that QIG-induced cytotoxicity associated with intracellular ROS accumulation which could suppress the AKT/mTOR signaling pathway, and then induce autophagy and inhibit cell growth. Besides, Erk signaling pathway was also involved in the process of autophagic cell death. Moreover, QIG extract also influenced EMT process and inhibited CRC cell migration. Conclusion Altogether, this study provides a basis for the utilization of QIG as an alternative medicine for CRC prevention and treatment.

scholarly journals Micronized sacchachitin promotes satellite cell proliferation through TAK1-JNK-AP-1 signaling pathway predominantly by TLR2 activation

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Meng-Huang Wu ◽  
Chuang-Yu Lin ◽  
Chun-Yin Hou ◽  
Ming-Thau Sheu ◽  
Hsi Chang
Keyword(s):  
Signaling Pathway ◽  
Tibialis Anterior ◽  
Neuromuscular Disorders ◽  
Underlying Mechanism ◽  
Signal Pathway ◽  
Growth Media ◽  
Muscle Stem Cells ◽  
Tlr2 Activation ◽  
Molecular Signal ◽  
First Time

Abstract Background Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damage but also strengthen the muscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin (mSC) on satellite cells (SCs), which are known as the muscle stem cells. Methods The myogenic cells, included SCs (Pax7+) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cultivated cells were immunostained with Pax7 and bromodeoxyuridine assessed simultaneously. The molecular signal pathway was further investigated by using Western blotting and signal pathway inhibitors. Results Our data revealed that 200 µg/mL mSC had an optimal capability to significantly enhance the SC proliferation. Furthermore, this enhancement of SC proliferation was verified to be involved with activation of TAK1-JNK-AP-1 signaling pathway through TLR2, whose expression on SC surface was confirmed for the first time here. Conclusion Micronized sacchachitin extracted from GT was capable of promoting the proliferation of SC under a correct concentration.

scholarly journals Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

2017 ◽  
Author(s):  
Min Hu ◽  
Yuehui Zhang ◽  
Jiaxing Feng ◽  
Xue Xu ◽  
Jiao Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Polycystic Ovary ◽  
Metformin Therapy ◽  
Before And After ◽  
Elevated Expression ◽  
Targeted Gene Expression ◽  
First Time

AbstractImpaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions.

scholarly journals Micronized sacchachitin promotes satellite cell proliferation through TAK1-JNK-AP-1 signaling pathway by TLR2/4 activation

2020 ◽  
Author(s):  
Meng-Huang Wu ◽  
Chuang-Yu Lin ◽  
Chun-Yin Hou ◽  
Ming-Thau Sheu ◽  
Hsi Chang
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Tibialis Anterior ◽  
Neuromuscular Disorders ◽  
Underlying Mechanism ◽  
Signal Pathway ◽  
Growth Media ◽  
Muscle Stem Cells ◽  
Molecular Signal ◽  
First Time

Abstract Background Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damage but also strengthen the muscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin (mSC) on satellite cells (SCs), which are known as the muscle stem cells. Methods The myogenic cells, included SCs (Pax7+) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cultivated cells were immunostained with Pax7 and bromodeoxyuridine assessed simultaneously. The molecular signal pathway was further investigated by using Western blotting and signal pathway inhibitors. Results Our results revealed that 200 µg/mL mSC had an optimal capability to significantly enhance the SC proliferation. Furthermore, this enhancement of SC proliferation was verified to be involved with activation of TAK1-JNK-AP-1 signaling pathway through TLR2, whose expression on SC surface was confirmed for the first time here. Conclusion Micronized sacchachitin extracted from GT was capable of promoting the proliferation of SC under a correct concentration.

scholarly journals Cucumis sativus L. Seeds Ameliorate Muscular Spasm-Induced Gastrointestinal and Respiratory Disorders by Simultaneously Inhibiting Calcium Mediated Signaling Pathway

2021 ◽  
Vol 14 (11) ◽  
pp. 1197
Author(s):  
Muqeet Wahid ◽  
Fatima Saqib ◽  
Hanadi Talal Ahmedah ◽  
Claudia Mihaela Gavris ◽  
Vincenzo De Feo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cucumis Sativus ◽  
Bioactive Compounds ◽  
In Silico ◽  
Target Genes ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Response Curves ◽  
Cucumis Sativus L ◽  
In Silico Studies

Cucumis sativus L. is globally cultivated as an edible vegetable. Besides its nutritional benefits, it is used in traditional medicines against various ailments. The current study was designed to elucidate the multi-target mechanisms of a C. sativus seeds extract against asthma and diarrhea using network pharmacology along with a molecular docking approach. Furthermore, in-vitro and in-vivo experiments were conducted to verify the mechanistic insight of in silico studies. LC-ESI-MS/MS was performed to identify the bioactive compounds in the extract; later, some compounds were quantified by HPLC. C. sativus seed. EtOH has kaempferol in higher concentration 783.02 µg/g, followed by quercetin (693.83 µg/g) and luteolin (617.17 µg/g). In silico studies showed that bioactive compounds interfered with asthma and diarrhea-associated target genes, which are members of calcium-mediated signaling to exert a calcium channel blocker activity. The seeds extract exerted a concentration-dependent spasmolytic response on isolated jejunum, trachea, and urinary bladder preparations and caused relaxation of spastic contraction of K+ (80 mM) with suppressed calcium concentration-response curves at dose 0.3 and 1 mg/mL. It also showed antiperistalsis, antidiarrheal and antisecretory activity in animal models. Thus, C. sativus seeds have therapeutic effects by regulating the contractile response through a calcium-mediated signaling pathway.

Exploring the Potential Mechanism of Shufeng Jiedu Capsule for Treating COVID-19 by Comprehensive Network Pharmacological Approaches and Molecular Docking Validation

2020 ◽  
Vol 23 ◽  
Author(s):  
Zhenjie Zhuang ◽  
Xiaoying Zhong ◽  
Huanhuan Zhang ◽  
Huiqi Chen ◽  
Boxiang Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Holistic View ◽  
Chinese Patent ◽  
Molecule Docking

Objective: Shufeng Jiedu capsule (SFJDC) is a well-known Chinese patent drug that is recommended as a basic prescription and applied widely in the clinical treatment of COVID-19. However, the exact molecular mechanism of SFJDC remains unclear. The present study aims to determine the potential pharmacological mechanisms of SFJDC in the treatment of COVID-19 based on network pharmacology. Methods: The network pharmacology-based strategy includes collection and analysis of active compounds and target genes, network construction, identification of key compounds and hub target genes, KEGG and GO enrichment, recognition and analysis of main modules, as well as molecule docking. Results: A total of 214 active chemical compounds and 339 target genes of SFJDC were collected. Of note, 5 key compounds ( β -sitosterol, luteolin, kaempferol, quercetin, and stigmasterol) and 10 hub target genes (TP53, AKT1, NCOA1, EGFR, PRKCA, ANXA1, CTNNB1, NCOA2, RELA and FOS) were identified based on network analysis. The hub target genes mainly enriched in pathways including MAPK signaling pathway, PI3K-Akt signaling pathway and cAMP signaling pathway, which could be the underlying pharmacological mechanisms of SFJDC for treating COVID-19. Moreover, the key compounds had high binding activity with three typical target genes. Conclusions: y network pharmacology analysis, SFJDC was found to effectively improve immune function and reduce inflammatory responses based on its key compounds, hub target genes, and the relevant pathways. These findings may provide valuable evidence for explaining how SFJDC exerting the therapeutic effects on COVID-19, providing a holistic view for further clinical application.

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.

Systematic Analysis of tRNA-Derived Small RNAs Reveals Effects of Xuefu-Zhuyu Decoction on Hippocampus of Rats after Traumatic Brain Injury

2021 ◽  
Author(s):  
Feng Dai ◽  
Tao Tang ◽  
Ruohuang Lu ◽  
Pengfei Li ◽  
Dandan Feng ◽  
...  
Keyword(s):  
Experimental Data ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Rat Model ◽  
Small Rnas ◽  
Target Genes ◽  
Cocaine Addiction ◽  
Therapeutic Effects ◽  
Xuefu Zhuyu Decoction

Abstract Background: Traumatic brain injury (TBI) is one of the most common neurosurgical diseases which refers to brain function impairment or brain pathological changes induced by external causes. A traditional Chinese medicine, Xuefu Zhuyu Decoction (XFZYD), has been indicated to harbor therapeutic property against TBI. Transfer RNA (tRNA)-derived small RNAs i.e., tsRNAs (a group of small RNAs derived from tRNAs) are multifunctional regulatory non-coding RNAs generated under pressure and implicated in the progression of TBI.Methods: TBI model was successfully constructed by using of rats. Further using sequencing and omics to identify novel tsRNAs as drug targets for XFZYD therapy against TBI in rat hippocampus. qPCR assay was used to further verify the experimental results. GO analyzed the signaling pathways of downstream target genes of tsRNA in XFZYD regulated TBI model. qPCR was used to detect the influence of over-expressed tsRNA mimic/inhibitor on their target genes in PC12 cell.Results: Our RNA-Seq data illustrates that 11 tsRNAs were mediated by the XFZYD. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment and nicotine pharmacodynamics pathway. We also confirm that Pi4kb, Mlh3, Pcdh9, and Ppp1cb were targets genes of 2 XFZYD regulated tsRNAs in hippocampus of rat model and PC12 cells. Furthermore, biological function analysis revealing potential therapeutic effects of tsRNAs, and results found Mapk1, Gnai1 was the related genes of for XFZYD therapy against TBI.Conclusion: Our work successfully illuminates the efficiency of XFZYD for the treatment of TBI. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment and nicotine pharmacodynamics pathway in TBI rat model.

scholarly journals Exploring the mechanism of aidi injection for lung cancer by network pharmacology approach and molecular docking validation

2021 ◽  
Vol 41 (2) ◽  
Author(s):  
Zhenjie Zhuang ◽  
Tong Lin ◽  
Lixia Luo ◽  
Weixin Zhou ◽  
Junmao Wen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Target Genes ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Hub Genes ◽  
Aidi Injection

Abstract Background. Aidi injection (ADI) is an effective Traditional Chinese medicine preparation widely used for lung cancer. However, the pharmacological mechanisms of ADI on lung cancer remain to be elucidated. Methods. A network pharmacology (NP)-based approach and the molecular docking validation were conducted to explore underlying mechanisms of ADI on lung cancer. The compounds and target genes were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (Batman-TCM) database. The STRING database was utilized for protein interaction network construction. The R package clusterProfiler was used for bioinformatics annotation of hub target genes. The gene expression analysis and survival analysis were performed based on The Cancer Genome Atlas (TCGA) database. The Autodock Vina was used for molecular docking validation. Results. A total of five key compounds with 324 putative target genes were screened out, and 14 hub target genes were identified for treating lung cancer. Six hub genes could influence the survival of non-small cell lung cancer (NSCLC) patients. Of these hub genes, the expression pattern of EGFR, MYC, PIK3CA, and SMAD3 were significantly higher in the LUSC, while PIK3CA and RELA expressed lower in the LUAD group and LUSC group, respectively. These six hub genes had good docking affinity with the key compounds of ADI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that ADI may exert therapeutic effects on lung cancer by regulating critical pathways including the thyroid hormone signaling pathway, MAPK signaling pathway, and PI3K-Akt signaling pathway. Conclusions. The present study explored the potential pharmacological mechanisms of ADI on lung cancer, promoting the clinical application of ADI in treating lung cancer, and providing references for advanced researches.

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