scholarly journals L-Leucine Alters Pancreatic  -Cell Differentiation and Function via the mTor Signaling Pathway

Diabetes ◽  
2011 ◽  
Vol 61 (2) ◽  
pp. 409-417 ◽  
Author(s):  
L. Rachdi ◽  
V. Aiello ◽  
B. Duvillie ◽  
R. Scharfmann
Keyword(s):  
Cell Differentiation ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Pancreatic Cell ◽  
And Function

scholarly journals Update on Atypicalities of Central Nervous System in Autism Spectrum Disorder

2020 ◽  
Vol 10 (5) ◽  
pp. 309
Author(s):  
Ahmad Naqib Shuid ◽  
Putri Ayu Jayusman ◽  
Nazrun Shuid ◽  
Juriza Ismail ◽  
Norazlin Kamal Nor ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Central Nervous System ◽  
Nervous System ◽  
Signaling Pathway ◽  
Immune Dysregulation ◽  
Autism Spectrum ◽  
Mtor Signaling ◽  
Spectrum Disorder ◽  
Mtor Signaling Pathway ◽  
And Function

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined, neurodevelopmental disorder that has been modeled as a brain-based disease. The behavioral and cognitive features of ASD are associated with pervasive atypicalities in the central nervous system (CNS). To date, the exact mechanisms underlying the pathophysiology of ASD still remain unknown and there is currently no cure or effective treatment for this disorder. Many publications implicated the association of ASD with inflammation, immune dysregulation, neurotransmission dysfunction, mitochondrial impairment and cell signaling dysregulation. This review attempts to highlight evidence of the major pathophysiology of ASD including abnormalities in the brain structure and function, neuroglial activation and neuroinflammation, glutamatergic neurotransmission, mitochondrial dysfunction and mechanistic target of rapamycin (mTOR) signaling pathway dysregulation. Molecular and cellular factors that contributed to the pathogenesis of ASD and how they may affect the development and function of CNS are compiled in this review. However, findings of published studies have been complicated by the fact that autism is a very heterogeneous disorder; hence, we addressed the limitations that led to discrepancies in the reported findings. This review emphasizes the need for future studies to control study variables such as sample size, gender, age range and intelligence quotient (IQ), all of which that could affect the study measurements. Neuroinflammation or immune dysregulation, microglial activation, genetically linked neurotransmission, mitochondrial dysfunctions and mTOR signaling pathway could be the primary targets for treating and preventing ASD. Further research is required to better understand the molecular causes and how they may contribute to the pathophysiology of ASD.

scholarly journals Cholesterol 25-Hydroxylase Promotes Osteogenesis and Suppresses Adipogenesis of Bone Marrow Stromal Cells via mTOR Signaling Pathway

2021 ◽  
Author(s):  
Haoran Li ◽  
Lei Zhou ◽  
Shiwei Sun ◽  
Tianlong Zhang ◽  
Wuling Zhou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Differentiation ◽  
Signaling Pathway ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Cholesterol Metabolism ◽  
Stem Cell Differentiation ◽  
Mtor Signaling ◽  
Marrow Stromal Cells ◽  
Mtor Signaling Pathway

Abstract Background Increased adipogenesis and reduced osteogenesis of bone marrow stromal cells (BMSCs) are key features of glucocorticoid-induced osteoporosis (GIOP). However, the mechanism of controlling the differentiation balance of bone marrow stromal cells (BMSCs) is still unclear. Recent years, studies on the relationship between cholesterol metabolism and bone metabolism have been increasing. Various cholesterol metabolism-related molecules have been proved to be involved in BMSCs differentiation. Cholesterol-25-Hydroxylase (CH25H) is a multi-transmembrane endoplasmic reticulum related enzyme which participated in various metabolic process, including immunity, stem cell differentiation and inflammation. Here we discovered and proved its role in regulating stem cell differentiation and explored the mechanism. Methods RNAi sequences or cDNA were designed to knockdown or overexpress CH25H in cells. Alkaline phosphatase (ALP), alizarin red S (AR-S) staining and Oil Red O staining were used to identify osteogenic or adipogenic differentiation ability of different cells. Meanwhile, biomarkers of osteogenesis or adipogenesis were tested by quantitative real time polymerase chain reaction (qRT-PCR) to quantify the degree of cell differentiation. Western blot was performed to detect the protein expression of CH25H and the key molecules of mTOR signaling pathway. Subcutaneous ectopic osteogenesis experiment in nude mice and immunohistochemistry (IHC) were applied to verify the results of in vitro experiments. Results CH25H could increase osteogenesis and suppress adipogenesis. Besides, the mTOR signaling pathway was found upregulated when knocking down CH25H. When using rapamycin, a specific inhibitor of mTOR, the regulating effect of osteo-adipogenic regulation were partly reversed. These results indicated that CH25H was a key regulator of BMSCs osteo-adipogenic differentiation and the mTOR signaling pathway was the downstream mechanism. Animal experiments have also got consistent results. Conclusion CH25H could promotes osteogenesis and suppresses adipogenesis of bone marrow stromal cells via mTOR signaling pathway.

l-Proline induces differentiation of ES cells: a novel role for an amino acid in the regulation of pluripotent cells in culture

2010 ◽  
Vol 298 (5) ◽  
pp. C982-C992 ◽  
Author(s):  
Jennifer M. Washington ◽  
Joy Rathjen ◽  
Fernando Felquer ◽  
Ana Lonic ◽  
Michael D. Bettess ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Differentiation ◽  
Signaling Pathway ◽  
Es Cells ◽  
Cell Formation ◽  
Embryonic Stem ◽  
Mtor Signaling ◽  
Cell Phenotype ◽  
Mtor Signaling Pathway

The development of cell therapeutics from embryonic stem (ES) cells will require technologies that direct cell differentiation to specific somatic cell lineages in response to defined factors. The initial step in formation of the somatic lineages from ES cells, differentiation to an intermediate, pluripotent primitive ectoderm-like cell, can be achieved in vitro by formation of early primitive ectoderm-like (EPL) cells in response to a biological activity contained within the conditioned medium MEDII. Fractionation of MEDII has identified two activities required for EPL cell formation, an activity with a molecular mass of <3 kDa and a second, much larger species. Here, we have identified the low-molecular-weight activity as l-proline. An inhibitor of l-proline uptake, glycine, prevented the differentiation of ES cells in response to MEDII. Supplementation of the culture medium of ES cells with >100 M l-proline and some l-proline-containing peptides resulted in changes in colony morphology, cell proliferation, gene expression, and differentiation kinetics consistent with differentiation toward a primitive ectoderm-like cell. This activity appeared to be associated with l-proline since other amino acids and analogs of proline did not exhibit an equivalent activity. Activation of the mammalian target of rapamycin (mTOR) signaling pathway was found to be necessary but not sufficient for l-proline activity; addition of other activators of the mTOR signaling pathway failed to alter the ES cell phenotype. This is the first report describing a role for amino acids in the regulation of pluripotency and cell differentiation and identifies a novel role for the imino acid l-proline.

The Modulation of Regulatory T Cells via High Mobility Group Box-1/Receptor for Advanced Glycation End-Products/Adenosine Monophosphate-Activated Protein Kinase Axis in Chronic Kidney Diseases with Complication of Sepsis

2021 ◽  
Vol 11 (11) ◽  
pp. 2298-2305
Author(s):  
Yingying Chen ◽  
Lan Chen ◽  
Yiyan Zhang ◽  
Yisheng Ling ◽  
Xiaolong Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Signaling Pathway ◽  
Kidney Diseases ◽  
Mtor Signaling ◽  
Jurkat Cells ◽  
Potential Mechanism ◽  
Mtor Signaling Pathway ◽  
Chronic Kidney Diseases ◽  
And Function

Chronic kidney diseases (CKD) with complication of sepsis brings great clinical burden worldwide. Regulatory T cells (Tregs) can regulate key immune response during the progression of the diseases. The present study aims to investigate the role of HMGB1 in the regulation of Tregs and find out the potential mechanism. Jurkat cells were stimulated with 0.5 ng/ml TGF-β1 for 24 h to induce phenotypic alternation into Tregs, followed by stimulation with indoxyl sulfate (IS) and lipopolysac-charide (LPS) for 24 h. Then, Tregs were treated with recombinant human HMBG1 (rHMGB1) at different concentrations (10, 100 and 1000 ng/ml). Cell viability of Tregs was assayed by CCK-8. The gene expressions related to proliferation and autophagy were determined using RT-qPCR and western blotting. RAGE was inhibited by transfection with shRNA-RAGE in Tregs. The results showed that HMGB1 and RAGE were upregulated upon IS and LPS induction in Tregs. rHMGB1 significantly promoted the viability, proliferation and function of Tregs at a concentration-dependent way, which was partly reversed by RAGE knockdown. Besides, HMGB1-RAGE could regulate autophagy activity and AMPK-mTOR signaling pathway. In summary, our study concluded that the active autophagy mediated by enhanced HMGB1-RAGE axis through AMPK-mTOR signaling pathway was a potential mechanism to enhance Tregs viability and function in chronic kidney diseases with complication of sepsis.

scholarly journals Roquin Suppresses the PI3K-mTOR Signaling Pathway to Inhibit T Helper Cell Differentiation and Conversion of Treg to Tfr Cells

Immunity ◽  
2017 ◽  
Vol 47 (6) ◽  
pp. 1067-1082.e12 ◽  
Author(s):  
Katharina Essig ◽  
Desheng Hu ◽  
Joao C. Guimaraes ◽  
Dominik Alterauge ◽  
Stephanie Edelmann ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
T Helper Cell ◽  
Helper Cell ◽  
Mtor Signaling Pathway ◽  
T Helper

UPF1 Impacts on mTOR Signaling Pathway and Autophagy in Endometrioid Endometrial Carcinoma

2020 ◽  
Author(s):  
Minfen Zhang ◽  
Hui Chen ◽  
Ping Qin ◽  
Tonghui Cai ◽  
Lingjun Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

Targeting mammalian target of rapamycin: prospects for the treatment of inflammatory bowel diseases

2020 ◽  
Vol 27 ◽  
Author(s):  
Naser-Aldin Lashgari ◽  
Nazanin Momeni Roudsari ◽  
Saeideh Momtaz ◽  
Negar Ghanaatian ◽  
Parichehr Kohansal ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
In Vivo Studies ◽  
Cochrane Library ◽  
Mtor Signaling Pathway ◽  
Inflammatory Bowel

: Inflammatory bowel disease (IBD) is a general term for a group of chronic and progressive disorders. Several cellular and biomolecular pathways are implicated in the pathogenesis of IBD, yet the etiology is unclear. Activation of the mammalian target of rapamycin (mTOR) pathway in the intestinal epithelial cells was also shown to induce inflammation. This review focuses on the inhibition of the mTOR signaling pathway and its potential application in treating IBD. We also provide an overview on plant-derived compounds that are beneficial for the IBD management through modulation of the mTOR pathway. Data were extracted from clinical, in vitro and in vivo studies published in English between 1995 and May 2019, which were collected from PubMed, Google Scholar, Scopus and Cochrane library databases. Results of various studies implied that inhibition of the mTOR signaling pathway downregulates the inflammatory processes and cytokines involved in IBD. In this context, a number of natural products might reverse the pathological features of the disease. Furthermore, mTOR provides a novel drug target for IBD. Comprehensive clinical studies are required to confirm the efficacy of mTOR inhibitors in treating IBD.

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