scholarly journals Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi-An Lin ◽  
Yan-Rong Li ◽  
Yi-Ching Chang ◽  
Mei-Chich Hsu ◽  
Szu-Tah Chen
Keyword(s):  
Mtor Inhibitor ◽  
Signal Pathway ◽  
C2c12 Cells ◽  
Signal Pathways ◽  
Heavy Chains ◽  
Regenerative Effect ◽  
Ampk Phosphorylation ◽  
Pre Treatment ◽  
Myotube Hypertrophy ◽  
C2c12 Myotube

AbstractThe regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways. C2C12 myotube hypertrophy was demonstrated by enlarged myotube and increased myosin heavy chains (MyHCs). In similar to IGF-1, EE/ICA activated key components of the IGF-1 signal pathway, including IGF-1 receptor. Pre-treatment with IGF-1 signal pathway specific inhibitors such as picropodophyllin, LY294002, and rapamycin attenuated EE induced myotube hypertrophy and MyHC isoform overexpression. In a different way, EE induced MHyC-S overexpression can be blocked by AMPK, but not by mTOR inhibitor. On the level of transcription, EE suppressed myostatin and MRF4 expression, but did not suppress atrogenes MAFbx and MuRF1 like IGF-1 did. Differential regulation of MyHC isoform and atrogenes is probably due to inequivalent AKT and AMPK phosphorylation induced by EE and IGF-1. These findings suggest that EE/ICA stimulates pathways partially overlapping with IGF-1 signaling pathway to promote myotube hypertrophy.

scholarly journals Ginsenoside Rg1 Prevents Doxorubicin-Induced Cardiotoxicity through the Inhibition of Autophagy and Endoplasmic Reticulum Stress in Mice

2018 ◽  
Vol 19 (11) ◽  
pp. 3658 ◽  
Author(s):  
Zhi-Meng Xu ◽  
Cheng-Bin Li ◽  
Qing-Ling Liu ◽  
Ping Li ◽  
Hua Yang
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Role ◽  
Primary Component ◽  
Signal Pathways ◽  
Ginsenoside Rg1 ◽  
Cellular Signal ◽  
Pre Treatment ◽  
Activating Transcription Factor ◽  
Doxorubicin Group

Ginsenoside Rg1, a saponin that is a primary component of ginseng, has been demonstrated to protect hearts from diverse cardiovascular diseases with regulating multiple cellular signal pathways. In the present study, we investigated the protective role of ginsenoside Rg1 on doxorubicin-induced cardiotoxicity and its effects on endoplasmic reticulum stress and autophagy. After pre-treatment with ginsenoside Rg1 (50 mg/kg i.g.) for 7 days, male C57BL/6J mice were intraperitoneally injected with a single dose of doxorubicin (6 mg/kg) every 3 days for four injections. Echocardiographic and pathological findings showed that ginsenoside Rg1 could significantly reduce the cardiotoxicity induced by doxorubicin. Ginsenoside Rg1 significantly inhibited doxorubicin-induced formation of autophagosome. At the same time, ginsenoside Rg1 decreased the doxorubicin-induced cardiac microtubule-associated protein-light chain 3 and autophagy related 5 expression. Ginsenoside Rg1 can reduce endoplasmic reticulum dilation caused by doxorubicin. Compared with the doxorubicin group, the expression of cleaved activating transcription factor 6 and inositol-requiring enzyme 1 decreased in group ginsenoside Rg1. Treatment with ginsenoside Rg1 reduces the expression of TIF1 and increases the expression of glucose-regulated protein 78. In the ginsenoside Rg1 group, the expression of p-P70S6K, c-Jun N-terminal kinases 1 and Beclin1 declined. These results indicate that ginsenoside Rg1 may improve doxorubicin-induced cardiac dysfunction by inhibiting endoplasmic reticulum stress and autophagy.

Prediction of Genes Regulated by JAK-STAT Signal Pathway

2013 ◽  
Vol 796 ◽  
pp. 25-35 ◽  
Author(s):  
Jia Bin Liu ◽  
Ying Qian ◽  
Ren Yu Xue ◽  
Guang Li Cao ◽  
Cheng Liang Gong
Keyword(s):  
Immune Response ◽  
Promoter Region ◽  
Promoter Sequence ◽  
Signal Pathway ◽  
Signal Pathways ◽  
Genome Database ◽  
Go Annotation ◽  
Promoter Sequences ◽  
Upstream Promoter ◽  
Cellular Immune

JAK-STAT signaling pathway shared by a variety of cytokines was discovered in recent years. It plays an important role in growth and development, cell apoptosis and immune response. In general, activated STAT dimer binds to a palindromic sequence (TTCN2-4GAA) located at the upstream promoter region to activate gene transcription. Some signal pathways including Toll and Imd in silkworm Bombyx mori, a model of Lepidopteran insect, have been well studied. However, little is known regarding JAK-STAT signal pathway. In the present study, the genes regulated by JAK-STAT signal pathway were predicted by bioinformatics analysis. 1000bp of upstream promoter sequence of the all predicted genes were downloaded from the silkworm genome database, and the STAT binding sequence TTCN2-4GAA were searched by scanning the promoter sequences, the results showed that 1 to 6 the target sequences could be found in the upstream promoter sequences of 9293 genes coding7271 non-redundant proteins. Go annotation results showed that these proteins were involved to cellular component, molecular function and biological process, suggesting JAK-STAT pathway play an important role in many way. More than 50% genes related to binding, about 40% genes related to cellular process, metabolic process and catalytic activity in the targeting genes. It is considered that JAK-STAT play a role in immune response.1-4 STAT binding sequences could be detected in promoter region of some genes related to anti-viral factors, cellular immune effector, and small antimicrobial peptide including defensin, attacin, moricin and gloverin3, implying that the expression of some anti-viral factors, cellular immune effectors and antimicrobial peptides related to antiviral activity might be regulated by JAK-STAT signal pathway.

scholarly journals C-Type Natriuretic Peptide Plays an Anti-Inflammatory Role in Rat Epididymitis Induced by UPEC

2021 ◽  
Vol 11 ◽  
Author(s):  
Chunlei Mei ◽  
Yafei Kang ◽  
Chenlu Zhang ◽  
Chunyu He ◽  
Aihua Liao ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Signal Pathway ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Signal Pathways ◽  
Inflammatory Damage ◽  
Cgmp Analog ◽  
Acute Epididymitis

Human epididymitis is mainly caused by retrograde urinary tract infection with uropathogenic Escherichia coli (UPEC). This disease is an important factor (accounting for 20–30%) causing male infertility. C-type natriuretic peptide (CNP), a protein composed of 22 amino acids, is proved to play an immunoregulatory role in respiratory and cardiovascular systems. CNP is expressed extremely high in the epididymis, but whether CNP plays the same role in acute epididymitis is unclear. At first, we established an acute caput epididymitis model in rats with UPEC and treated them with CNP to measure inflammatory damage. Then RNA-seq transcriptome technology was used to reveal potential signal pathways. Secondly, the turbidity and activity of UPEC were assessed using a microplate reader and the amount of UPEC by agar plates after incubation with CNP. Thirdly, macrophages in caput epididymis were tested by immunohistochemistry (IHC). Meanwhile, lipopolysaccharide (LPS) with or without CNP was used to stimulate the macrophage (RAW264.7) in vitro and to detect the expression level of pro-inflammatory factors. Finally, the macrophage (RAW264.7) was treated with CNP, 8-Br-cGMP [cyclic guanosinc monophosphate (cGMP) analog] and KT5823 [protein kinase G (PKG) inhibitor], and the expression level of nuclear factor-k-gene binding (NF-kB) signal pathway was examined. The results showed that the damage of epididymis induced by UPEC as well as the pro-inflammatory factors could be alleviated significantly with CNP treatment. CNP could inhibit the activity and numbers of bacteria in both in vivo and in vitro experiments. Moreover, CNP repressed the invasion, and the expression of pro-inflammatory factors (such as NF-kB, IL-1β, IL-6, TNF-α) in macrophages and its effect could be inhibited by KT5823. Therefore, we drew a conclusion from the above experiments that CNP alleviates the acute epididymitis injury induced by UPEC. On one hand, CNP could inhibit the growth of UPEC. On the other hand, CNP could decrease invasion and inflammatory reaction of macrophages; the mechanism was involved in inhibiting NF-kB signal pathway through the cGMP/PKG in macrophages. This research would open up the possibility of using CNP as a potential treatment for epididymitis.

scholarly journals Cell-free DNA fragments increase transcription in human mesenchymal stem cells, activate tlr-dependent signal pathway and supress apoptosis

2012 ◽  
Vol 58 (6) ◽  
pp. 673-683 ◽  
Author(s):  
S.V. Kostyuk ◽  
E.M. Malinovskaya ◽  
A.V. Ermakov ◽  
T.D. Smirnova ◽  
L.V. Kameneva ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Functional Activity ◽  
Human Mesenchymal Stem Cells ◽  
Signal Pathway ◽  
Signal Pathways ◽  
Dna Fragments ◽  
Cell Free Dna ◽  
Free Dna ◽  
Dependent Signal

Human mesenchymal stem cells (MSCs) are now widely adopted in regenerative medicine. However, many questions on the role of different signaling pathways in the regulation of stem cell (SC) functional activity within the organism remain unaswered. In damaged regions the level of cell death increases and DNA fragments from dead cells (cell-free DNA, cfDNA) are accumulated in blood. We showed that in adipose-derived MSCs exposed in vitro to cfDNA fragments the transcription level increased (the total amount of cellular RNA and the rRNA amount rose). GC-rich CfDNA fragments (GC-DNA) activated the TLR9-dependent signal pathway: the expression of TLR9 and of TLR9-signaling pathway adapter - MyD88 - was up-regulated. AT-rich DNA fragments did not increase the TLR9 expression, though, the MyD88 expression level rose. So we suggest that AT-DNA acts via some other receptors that nevertheless activate MyD88-dependent signalling in MSCs. We also showed that cfDNA fragments decreased the activity of caspase, an apoptotic enzyme. So, cfDNA can significantly influence the functional activity of MSC by activating TLR9- and MyD88-dependent signal pathways and lowering the apoptosis level.

scholarly journals Ganoderma microsporum immunomodulatory protein, GMI, promotes C2C12 myoblast differentiation in vitro via upregulation of Tid1 and STAT3 acetylation

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244791
Author(s):  
Wan-Huai Teo ◽  
Jeng-Fan Lo ◽  
Yu-Ning Fan ◽  
Chih-Yang Huang ◽  
Tung-Fu Huang
Keyword(s):  
Myogenic Differentiation ◽  
Atp Synthesis ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Muscle Loss ◽  
C2c12 Myoblasts ◽  
Immunomodulatory Protein ◽  
Pre Treatment

Ageing and chronic diseases lead to muscle loss and impair the regeneration of skeletal muscle. Thus, it’s crucial to seek for effective intervention to improve the muscle regeneration. Tid1, a mitochondrial co-chaperone, is important to maintain mitochondrial membrane potential and ATP synthesis. Previously, we demonstrated that mice with skeletal muscular specific Tid1 deficiency displayed muscular dystrophy and postnatal lethality. Tid1 can interact with STAT3 protein, which also plays an important role during myogenesis. In this study, we used GMI, immunomodulatory protein of Ganoderma microsporum, as an inducer in C2C12 myoblast differentiation. We observed that GMI pretreatment promoted the myogenic differentiation of C2C12 myoblasts. We also showed that the upregulation of mitochondria protein Tid1 with the GMI pre-treatment promoted myogenic differentiation ability of C2C12 cells. Strikingly, we observed the concomitant elevation of STAT3 acetylation (Ac-STAT3) during C2C12 myogenesis. Our study suggests that GMI promotes the myogenic differentiation through the activation of Tid1 and Ac-STAT3.

scholarly journals Investigation of Anti-osteoporosis Mechanisms of Rehmanniae Radix Preparata Based on Network Pharmacology and Experimental Verification

2021 ◽  
Author(s):  
Li Ou ◽  
Wenqian Kang ◽  
Ziyi Liang ◽  
Feng Gao ◽  
Taiwei Dong ◽  
...  
Keyword(s):  
Topological Analysis ◽  
Animal Experiments ◽  
Binding Activity ◽  
Signal Pathway ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Treatment Of Osteoporosis ◽  
Key Genes ◽  
Rehmanniae Radix

Abstract Background: Rehmanniae Radix Preparata (RRP) can effectively improve the symptoms of osteoporosis, but its molecular mechanism for treating osteoporosis is still unclear. The objective of this study is to investigate anti-osteoporosis mechanisms of RRP through network pharmacology.Methods: The overlapping targets of RRP and osteoporosis were screened out using online platforms. A visual network diagram of PPI was constructed and analyzed by Cytoscape 3.7.2 software. Molecular docking was used to evaluate the binding activity of ligands and receptors, and some key genes were randomly verified through pharmacological experiments. Results: According to topological analysis results, AKT1, MAPK1, ESR1, SRC, and MMP9 are key genes for RRP to treat osteoporosis, and they have high binding activity with stigmasterol and sitosterol. The main signal pathways of RRP in the treatment of osteoporosis, including Estrogen signaling pathway, HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway, etc. Results of animal experiments showed that RRP could significantly increase the expression levels of Akt1, ESR1 and SRC-1 mRNA in bone tissue to promote bone formation. Conclusion: This study explained the coordination between multiple components and multiple targets of RRP in the treatment of osteoporosis, and provided new ideas and basis for its clinical application and experimental research.

scholarly journals Kechuangping Mixture Inhibits LPS‑induced Macrophage Immune Response Through Suppressing the TLR4/MyD88/NF-κB Signal Pathway

2021 ◽  
Author(s):  
Shuang Lyu ◽  
Luo Liangtao ◽  
Aijun Yang ◽  
Lijun Yang ◽  
Hong Cui
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
Quantitative Polymerase Chain Reaction ◽  
Inhibitory Effect ◽  
Inflammatory Factors ◽  
Signal Pathways ◽  
Raw264.7 Macrophages ◽  
Macrophages Polarization ◽  
Potent Inhibitory Effect ◽  
Pre Treatment

Abstract Background: Kechuangping mixture (KCPM) based on Maxingshigan decoction has a significant clinical effect in the treatment of pediatric pneumonia, especially for asthmatic pneumonia. This study explored the effects of KCPM on lipopolysaccharide (LPS)-induced macrophage immune response and the molecular mechanism involved. Methods: CCK-8 assays was used to detect the effect of KCPM on cell viability. The RAW 264.7 macrophages were divided into four groups: blank, LPS, KCPM, LPS+KCPM. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to examine the secretion of inflammatory factors and the expression of TLR4/MyD88/NF-κB signal pathways with or without KCPM stimulation. Results: KCPM inhibited the differentiation of RAW264.7 macrophages induced by LPS. The secretion of pro-inflammatory cytokines IL-6 and TNF-α induced by LPS was decreased by pre-treatment with KCPM. While, treatment with KCPM advanced, the anti-inflammatory cytokines IL-10 and TGF-β increased significantly. Additionally, KCPM exhibited a potent inhibitory effect on the expression of iNOS and a promotive effect on the expression of Arg-1. Moreover, KCPM clearly suppressed the transcription level of TLR4, MyD88 and NF-κB signal pathways.Conclusion: KCPM promoted the macrophages polarization toward to M2 phenotype, as a result, limited the macrophage immune response. TLR4/MyD88/NF-κB signal pathways may play an important role in this process.

Differentially expressed circRNA and mRNA profiles of neural stem cells with radiation irradiation

2020 ◽  
Author(s):  
Zhaopeng Cai ◽  
Shan Wang ◽  
Zhongyu Xie ◽  
Peng Wang ◽  
Huiyong Shen ◽  
...  
Keyword(s):  
Regulatory Mechanism ◽  
Circular Rna ◽  
Signal Pathway ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Spine Metastasis ◽  
Radiation Induced ◽  
Differentially Expressed Mrna ◽  
Oncology Practice ◽  
Mapk Signal Pathway

Abstract Background Spine metastasis is common but highly problematic in clinical oncology practice. Radiotherapy plays an important role in the treatment of spine metastasis, but it at the same time damages the nervous tissue, especially the neural stem cell (NSC), and leads to radiation induced myelopathy. Circular RNA (circRNA) is a kind of non-coding RNA which responses to external stimulus and regulates cellular functions. However, the mechanism of radiotherapy affecting NSC and the role of circRNA in this process are still unclear. Methods The circRNA and mRNA of NSC treated with radiation or not were detect using next-generation sequencing. RT-PCR assays were preformed to confirm the sequencing results and the feature of differentially expressed circRNA. Bioinformation analyses were conducted to identified the critical circRNA and mRNA, as well as the enriched functions and pathways. Moreover, a circRNA-miRNA-mRNA network was constructed to investigate the possible regulatory mechanism. Results A total of 421 differentially expressed circRNA and 1602 differentially expressed mRNA of NSC were identified after radiotherapy. The GO and KEGG analysis of the differentially expressed mRNA as well as the host genes of the differentially expressed circRNA were performed and several key signal pathways such as MAPK signal pathway were identified. Moreover, a circRNA-miRNA-mRNA network focusing on MAPK signal pathway was shown and predicted that chr5:127160496|127165240 could be the critical circRNA in the regulatory mechanism of radiation treated NSCs. Conclusion Our finding showed the differentially expressed circRNA and mRNA profiles of NSC after radiotherapy, suggesting that circRNA may contribute to the pathogenesis of radiation induced myelopathy.

scholarly journals The negative charge of the 343 site is essential for maintaining physiological functions of CXCR4

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Liqing Wang ◽  
Qiuhong Xiong ◽  
Ping Li ◽  
Guangxin Chen ◽  
Nayab Tariq ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Glutamic Acid ◽  
Missense Mutation ◽  
Negative Charge ◽  
Signal Pathway ◽  
Signal Pathways ◽  
Phosphorylation Sites ◽  
Whim Syndrome ◽  
C Terminus ◽  
Hela Cell Lines

Abstract Background Warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathexis (WHIM) syndrome is a primary immunodeficiency disease (PID) usually caused by autosomal dominant mutations in the chemokine receptor CXCR4 gene. To date, a total of nine different mutations including eight truncation mutations and one missense mutation (E343K, CXCR4E343K) distributed in the C-terminus of CXCR4 have been identified in humans. Studies have clarified that the loss of phosphorylation sites in the C-terminus of truncated CXCR4 impairs the desensitization process, enhances the activation of G-protein, prolongs downstream signaling pathways and introduces over immune responses, thereby causing WHIM syndrome. So far, there is only one reported case of WHIM syndrome with a missense mutation, CXCR4E343K, which has a full length of C-terminus with entire phosphorylation sites, no change in all potential phosphorylation sites. The mechanism of the missense mutation (CXCR4E343K) causing WHIM syndrome is unknown. This study aimed to characterize the effect of mutation at the 343 site of CXCR4 causing the replacement of arginine/E with glutamic acid/K on the receptor signal transduction, and elucidate the mechanism underling CXCR4E343K causing WHIM in the reported family. Results We completed a series of mutagenesis to generate different mutations at the 343 site of CXCR4 tail, and established a series of HeLa cell lines stably expressing CXCR4WT or CXCR4E343D (glutamic acid/E replaced with aspartic acid/D) or CXCR4E343K (glutamic acid/E replaced with lysine/K) or CXCR4E343R (glutamic acid/E replaced with arginine/R) or CXCR4E343A (glutamic acid/E replaced with alanine/A) and then systematically analyzed functions of the CXCR4 mutants above. Results showed that the cells overexpressing of CXCR4E343D had no functional changes with comparison that of wild type CXCR4. However, the cells overexpressing of CXCR4E343K or CXCR4E343R or CXCR4E343A had enhanced cell migration, prolonged the phosphorylation of ERK1/2, p38, JNK1/2/3, aggravated activation of PI3K/AKT/NF-κB signal pathway, introduced higher expression of TNFa and IL6, suggesting over immune response occurred in CXCR4 mutants with charge change at the 343 site of receptor tail, as a result, causing WHIM syndrome. Biochemical analysis of those mutations at the 343 site of CXCR4 above shows that CXCR4 mutants with no matter positive or neutral charge have aberrant signal pathways downstream of activated mutated CXCR4, only CXVR4 with negative charge residues at the site shows normal signal pathway post activation with stromal-derived factor (SDF1, also known as CXCL12). Conclusion Taken together, our results demonstrated that the negative charge at the 343 site of CXCR4 plays an essential role in regulating the down-stream signal transduction of CXCR4 for physiological events, and residue charge changes, no matter positive or neutral introduce aberrant activities and functions of CXCR4, thus consequently lead to WHIM syndrome.

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