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

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.

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

10.21203/rs.3.rs-33099/v2 ◽

2020 ◽

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 damagebut also strengthen themuscle 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 bromodeoxyuridineassessed 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 sacchachitinextracted fromGT was capable of promoting the proliferation of SC under a correct concentration.

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

10.21203/rs.3.rs-33099/v3 ◽

2020 ◽

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 damagebut also strengthen themuscle 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 bromodeoxyuridineassessed 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 sacchachitinextracted fromGT was capable of promoting the proliferation of SC under a correct concentration.

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

10.21203/rs.3.rs-33099/v1 ◽

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.

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

AJP Cell Physiology ◽

10.1152/ajpcell.00232.2016 ◽

2017 ◽

Vol 313 (1) ◽

pp. C80-C93 ◽

Cited By ~ 15

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.

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

Cancers ◽

10.3390/cancers13092174 ◽

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.

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lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22031407 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1407

Author(s):

Hongxia Liu ◽

Wang Zheng ◽

Qianping Chen ◽

Yuchuan Zhou ◽

Yan Pan ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cell Line ◽

Malignant Tumors ◽

Underlying Mechanism ◽

Mtor Pathway ◽

Rna Seq ◽

Cellular Autophagy ◽

First Time

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

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Correction to: Micronized sacchachitin promotes satellite cell proliferation through TAK1-JNK-AP-1 signaling pathway predominantly by TLR2 activation

Chinese Medicine ◽

10.1186/s13020-020-00420-z ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Meng–Huang Wu ◽

Chuang–Yu Lin ◽

Chun–Yin Hou ◽

Ming–Thau Sheu ◽

Hsi Chang

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Satellite Cell ◽

Tlr2 Activation ◽

Satellite Cell Proliferation

An amendment to this paper has been published and can be accessed via the original article.

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

Alcohol and Alcoholism ◽

10.1093/alcalc/agab065 ◽

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.

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CHARACTERISTICS OF AGE-DEPENDENT CHANGES IN THE URINE'S PROTEOM COMPOSITION OF THE HEALTHY PERSONS (EXPERIMENTAL AND THEORETICAL STUDY)

Успехи геронтологии ◽

10.34922/ae.2020.33.4.016 ◽

2020 ◽

pp. 735-740

Author(s):

Л. Х. Пастушкова ◽

Д. Н. Каширина ◽

А. Г. Гончарова ◽

Н. Б. Захарова ◽

Е. С. Тийс ◽

...

Keyword(s):

Signaling Pathway ◽

Insulin Signaling ◽

Defense Mechanisms ◽

Theoretical Study ◽

Clinical Manifestations ◽

Age Dependent ◽

First Time ◽

Healthy Persons ◽

Over Time

Впервые описаны белки, достоверно увеличивающиеся и уменьшающиеся в моче с возрастом в интервале 20-60 лет. Охарактеризованы комбинации белков, связанных с изменением иммунных процессов, нарушением реологии крови, в том числе риском коагулопатии, противоопухолевых защитных механизмов, инсулинового сигнального пути, с изменением характеристик клеточного деления и качества новообразованной ткани. Таким образом, возрастная динамика основных процессов запускает каскад реакций, проявляющихся в замыкании «патологических биохимических кругов», которые формируют предпосылки к развитию заболеваний и, с течением времени, клинические проявления. For the ﬁrst time proteins are described, reliably increasing and decreasing in urine with age in the range of 20 to 60 years. The combinations of proteins associated with changes in immune processes, violation of blood reology, including the risk of coagulopathy, anticancer defense mechanisms, insulin signaling pathway, changes in cell characteristics are characterized division and quality of the newly formed fabric. Thus, the age dynamics of the main processes triggers a cascade of reactions manifested in the closure of «pathological biochemical circles» that form the prerequisites for the development of diseases and, over time, clinical manifestations.

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Muscle contracture and passive mechanics in cerebral palsy

Journal of Applied Physiology ◽

10.1152/japplphysiol.00278.2018 ◽

2019 ◽

Vol 126 (5) ◽

pp. 1492-1501 ◽

Cited By ~ 15

Author(s):

Richard L. Lieber ◽

Jan Fridén

Keyword(s):

Extracellular Matrix ◽

Cerebral Palsy ◽

Satellite Cells ◽

Neuromuscular Disorders ◽

Light And Electron Microscopy ◽

Cell Types ◽

Underlying Mechanism ◽

Muscle Stiffness ◽

Muscle Satellite Cells ◽

Cord Injury

Skeletal muscle contractures represent the permanent shortening of a muscle-tendon unit, resulting in loss of elasticity and, in extreme cases, joint deformation. They may result from cerebral palsy, spinal cord injury, stroke, muscular dystrophy, and other neuromuscular disorders. Contractures are the prototypic and most severe clinical presentation of increased passive mechanical muscle force in humans, often requiring surgical correction. Intraoperative experiments demonstrate that high muscle passive force is associated with sarcomeres that are abnormally stretched, although otherwise normal, with fewer sarcomeres in series. Furthermore, changes in the amount and arrangement of collagen in the extracellular matrix also increase muscle stiffness. Structural light and electron microscopy studies demonstrate that large bundles of collagen, referred to as perimysial cables, may be responsible for this increased stiffness and are regulated by interaction of a number of cell types within the extracellular matrix. Loss of muscle satellite cells may be related to changes in both sarcomeres and extracellular matrix. Future studies are required to determine the underlying mechanism for changes in muscle satellite cells and their relationship (if any) to contracture. A more complete understanding of this mechanism may lead to effective nonsurgical treatments to relieve and even prevent muscle contractures.

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