scholarly journals Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

2020 ◽  
Vol 21 (6) ◽  
pp. 2252 ◽  
Author(s):  
Tamara Camino ◽  
Lago-Baameiro Nerea ◽  
Bravo Belén ◽  
Sueiro Aurelio ◽  
Couto Iván ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Metabolic Diseases ◽  
Cell Communication ◽  
Cell Of Origin ◽  
Insulin Resistant ◽  
Cell Tissue ◽  
Theoretical Mass ◽  
Adipocyte Cell ◽  
Related Proteins

Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNFα expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.

scholarly journals Medicinal Leech CNS as a Model for Exosome Studies in the Crosstalk between Microglia and Neurons

2018 ◽  
Vol 19 (12) ◽  
pp. 4124 ◽  
Author(s):  
Antonella Raffo-Romero ◽  
Tanina Arab ◽  
Issa Al-Amri ◽  
Francoise Le Marrec-Croq ◽  
Christelle Van Camp ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Present Report ◽  
Primary Cultures ◽  
Cell Communication ◽  
Medicinal Leech ◽  
Neuronal Cultures ◽  
Primary Neuronal Cultures ◽  
A Cell

In healthy or pathological brains, the neuroinflammatory state is supported by a strong communication involving microglia and neurons. Recent studies indicate that extracellular vesicles (EVs), including exosomes and microvesicles, play a key role in the physiological interactions between cells allowing central nervous system (CNS) development and/or integrity. The present report used medicinal leech CNS to investigate microglia/neuron crosstalk from ex vivo approaches as well as primary cultures. The results demonstrated a large production of exosomes from microglia. Their incubation to primary neuronal cultures showed a strong interaction with neurites. In addition, neurite outgrowth assays demonstrated microglia exosomes to exhibit significant neurotrophic activities using at least a Transforming Growth Factor beta (TGF-β) family member, called nGDF (nervous Growth/Differentiation Factor). Of interest, the results also showed an EV-mediated dialog between leech microglia and rat cells highlighting this communication to be more a matter of molecules than of species. Taken together, the present report brings a new insight into the microglia/neuron crosstalk in CNS and would help deciphering the molecular evolution of such a cell communication in brain.

scholarly journals The role of inhibins and activins in prostate cancer pathogenesis.

2000 ◽  
pp. 243-256 ◽  
Author(s):  
C R Dowling ◽  
G P Risbridger
Keyword(s):  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Prostate Gland ◽  
Prostate Carcinogenesis ◽  
Cancer Pathogenesis ◽  
Number Of Patients ◽  
Related Proteins

Successful prostate cancer diagnosis and management continue to provide challenges for the clinician. While interventions aimed at the containment of both early and late disease continue to fail in a significant number of patients, the search for answers must incorporate an analysis of the processes of normal and aberrant growth and development within the gland itself. Inhibin and its structurally related protein, activin, are members of the transforming-growth-factor beta (TGFbeta) superfamily. Originally identified as regulators of FSH, these proteins are now recognised to have widespread biological functions. This might be expected of proteins that are structurally homologous to TGFbeta itself, which is recognised to have regulatory roles in both normal and malignant prostate tissue. The aim of this review is to examine the relationship between inhibins, activins and their related proteins and the development of prostate cancer. The homology with TGF, the pluripotent effects of activin on various tissues and the roles for inhibins in ovarian cancer make activins and inhibins candidate growth factors for involvement at multiple sites in the progression from benign disease to cancer. In compiling this review, we aim to delineate the changes in inhibins and activins in this pathway and in doing so implicate their potential roles in the progression of carcinogenesis. We will compare the changes in inhibin and its related proteins in prostate cancer to those that are known in ovarian cancer. We will discuss the similarities and differences between the putative role of activins and TGFbeta in prostate carcinogenesis. The importance of this review lies in demonstrating that inhibin, an endocrine hormone, and its related proteins may contribute to endocrine-related cancers, such as that of the prostate gland.

scholarly journals Thrombospondin 1 in Metabolic Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Linda S. Gutierrez ◽  
Jovita Gutierrez
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Metabolic Diseases ◽  
Cell Metabolism ◽  
Matricellular Protein ◽  
Published Data ◽  
Obesity And Diabetes ◽  
Thrombospondin 1 ◽  
Cancer And Inflammation

The thrombospondin family comprises of five multifunctional glycoproteins, whose best-studied member is thrombospondin 1 (TSP1). This matricellular protein is a potent antiangiogenic agent that inhibits endothelial migration and proliferation, and induces endothelial apoptosis. Studies have demonstrated a regulatory role of TSP1 in cell migration and in activation of the latent transforming growth factor beta 1 (TGFβ1). These functions of TSP1 translate into its broad modulation of immune processes. Further, imbalances in immune regulation have been increasingly linked to pathological conditions such as obesity and diabetes mellitus. While most studies in the past have focused on the role of TSP1 in cancer and inflammation, recently published data have revealed new insights about the role of TSP1 in physiological and metabolic disorders. Here, we highlight recent findings that associate TSP1 and its receptors to obesity, diabetes, and cardiovascular diseases. TSP1 regulates nitric oxide, activates latent TGFβ1, and interacts with receptors CD36 and CD47, to play an important role in cell metabolism. Thus, TSP1 and its major receptors may be considered a potential therapeutic target for metabolic diseases.

Reduced Levels of mTOR and TGF- β Signaling Pathway-Associated Proteins in Patients with High Risk MDSsamia AL-Shouli. , Pilar Perezabellan, Frederic Toulza. Shahram Kordasti, Ghulam Mufti

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5501-5501
Author(s):  
Samia Towfeek Al-Shouli ◽  
Ghulam J Mufti
Keyword(s):  
T Cells ◽  
High Risk ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Cd4 T Cells ◽  
Transforming Growth Factor ◽  
Conflicts Of Interest ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Related Proteins

Abstract Background: T cell mediated immune dysregulation is an important feature of MDS. The expansion of regulatory T cells (Tregs) is one of the important factors in the progression of intermediate/high risk myelodysplastic syndrome (MDS) to acute myeloid leukemia. However, the exact mechanism for the expansion of Tregs in MDS is not known. Intracellular complements (particularly C3a and C5a) play a crucial role in the polarization of CD4+ T cells toward regulatory or effector phenotypes through Transforming growth factor-beta (TGF-β) pathway (C5aR2 mediated) or Mammalian Target of Rapamycin (mTOR)(C5aR mediated) respectively. The aim of this study was to investigate the potential role of mTOR and Akt as important proteins in complement related polarization of CD4+ T cells toward pro-inflammatory T helper cells in MDS. We have also studied the TGF-β signaling pathway related proteins, which are crucial for the expansion of Tregs. We investigated the level of TGF- β related proteins (phosphorylated (p) SMADs), as well as mTORc and Akt (Ser473) in high risk MDS and healthy donors (HD) before and after stimulation with CD3 and CD46 as a complement related co-stimulatory molecule. Methods: Peripheral blood mononuclear cell (PBMCs) from healthy controls and high-risk MDS patients were used for this study. Anti-CD3 (2.0 µg/mL), anti-CD28 (3.0 µg/mL) and/or anti-CD46 (2.0 µg/mL) antibodies were used to stimulate cells. The total protein was extracted by Bicinchoninic Acid (BCA) assay and quantified by nano-drop. The MILLIPLEX MAP Human TGF-β Signaling Magnetic Bead Panel 6-plex was used to detect the signaling changes in cell lysates using the Luminex® system following the manufacturer's instructions. Data were analysed using Microsoft Excel and expressed in means and standards deviation. The students T-test were used to assess the difference in means between groups. Results: TGF-β signaling pathway proteins pSMAD2, pSMAD3 and pSMAD4 as well as mTORc were evaluated. Unstimulated PBMCs from high-risk MDS patients showed a significantly lower level of m-TOR (p=0.01), pSMAD2 (p=0.01), pSMAD3 (p=0.02) and pSMAD4 (p=0.044) as compared to healthy donors. Following stimulation with anti-CD3±CD46 for 24 hours, there was no significant increase in protein levels of mTORc or Akt. However, in high-risk MDS patients the level of pSMAD2 (p=0.02) and pSMAD4 (p=0.006) remain significantly lower than healthy donors after 24 hours of stimulation with anti-CD3 and CD46. An aliquot of cells were used for flowcytometry following stimulation. Interestingly Tregs phenotype CD4+CD25highCD127lowexpressed higher level of intracellular C5aR2 in MDS (n=5) compared to HD (n=5). Conclusion: mTORc protein level in MDS is reduced and does not change in response to complement receptor stimulation neither does the level of Akt. This may prevent T cells to polarize toward pro-inflammatory T cells (Th1 or Th17) therefore avert an effective immune-surveillance against malignant clone. Lack of response to complement related co-stimulation and increase in C5aR2 expression suggest a potential mechanism for Treg expansion in MDS. These findings may lead to identification of new therapeutic targets in MDS, although need further studies on larger cohort of patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Matrine Ameliorates Colorectal Cancer in Rats via Inhibition of HMGB1 Signaling and Downregulation of IL-6, TNF-α, and HMGB1

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Huizhen Fan ◽  
Chunyan Jiang ◽  
Baoyuan Zhong ◽  
Jianwen Sheng ◽  
Ting Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
High Mobility ◽  
26S Proteasome ◽  
Network Pharmacology ◽  
Necrosis Factor Alpha ◽  
Elevated Expression ◽  
Underlying Mechanisms ◽  
Related Proteins

Matrine may be protective against colorectal cancer (CRC), but how it may work is unclear. Thus, we explored the underlying mechanisms of matrine in CRC. Matrine-related proteins and CRC-related genes and therapeutic targets of matrine in CRC were predicted using a network pharmacology approach. Five targets, including interleukin 6 (IL-6), the 26S proteasome, tumor necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1) and p53, and corresponding high-mobility group box 1 (HMGB1) signaling and T helper cell differentiation were thought to be associated with matrine’s mechanism. Expression of predicted serum targets were verified in a 1,2-dimethylhydrazine dihydrochloride-induced CRC model rats that were treated with matrine (ip) for 18 weeks. Data show that matrine suppressed CRC growth and decreased previously elevated expression of IL-6, TNF-α, p53, and HMGB1. Matrine may have had a therapeutic effect on CRC via inhibition of HMGB1 signaling, and this occurred through downregulation of IL-6, TNF-α, and HMGB1.

Growth-factor-related proteins that are inducers in early amphibian development may mediate similar steps in amniote (bird) embryogenesis

Development ◽  
1991 ◽  
Vol 111 (1) ◽  
pp. 197-212
Author(s):  
J. Cooke ◽  
A. Wong
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Normal Development ◽  
Tgf Beta ◽  
A Cell ◽  
Growth Factor Beta ◽  
Beta 2 ◽  
Related Proteins

Xenopus and murine activin A homologues (XTC-MIF and WEHI-MIF) and Xenopus and bovine basic fibroblast growth factor (bFGFs) are potent inducers of mesodermal and endodermal pathways of development in amphibian blastular animal cap cells. Porcine transforming growth factor beta 2 (TGF beta 2) is a weaker inducer in the same assay but human platelet-derived growth factor (PDGF) is inactive. We have assayed these factors for evidence of homologous effects in bird development. Unlike amphibians, bird embryos never exhibit a clean segregation of a cell layer that has a uniform specification when uninduced, and can be cultured in isolation as an assay after exposure to soluble factors. We have therefore performed less direct experiments, of three types. We have briefly cultured early chick epiblast cells with and without factors and then assayed their capacity to attach and spread upon fibronectin, in comparison with young streak and substreak hypoblast cells. We have asked whether similar microculture with factors alters the ability of quail epiblast cells to disrupt morphogenesis, and to integrate into the structure, of host chick blastoderms into which they are seeded. Finally, whole early chick blastoderms have been preincubated with or without factors for a brief period before setting them up to develop in vitro under circumstances usually permitting successful formation of axial pattern. Strong effects of the activin-like factors, of bFGF and of TGF beta 2 were seen in all three procedures, while PDGF was essentially inactive. In epiblast cells, effective factors at picomolar concentrations induced stable spreading upon fibronectin, and a capacity to adhere and spread upon basal epiblast surface and prevent morphogenesis in host blastoderms. Preincubation of whole early blastoderms with these factors led to characteristic deviation from normal development over the subsequent 24 h. We therefore suggest that peptides from the particular families that are active as inducers in amphibian blastula ectoderm may mediate homologous or closely related steps in respecification throughout vertebrates.

scholarly journals Angiogenesis in Patients with Chronic Heart Failure: Focus on Endothelial Vascular Growth Factor, Pentraxin-3 and Transforming Growth Factor Beta

2020 ◽  
Vol 16 (3) ◽  
pp. 439-448
Author(s):  
R. N. Shepel ◽  
O. M. Drapkina
Keyword(s):  
Heart Failure ◽  
Growth Factor ◽  
Chronic Heart Failure ◽  
Biological Markers ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Metabolic Diseases ◽  
Pentraxin 3 ◽  
Vascular Growth Factor ◽  
Growth Factor Beta

Chronic heart failure (CHF) is considered the leading cause of death in patients with established cardiovascular (CVD) and metabolic diseases. Although the current treatment strategy has improved survival and clinical outcomes, the prevalence of CHF shows an increase. Current clinical guidelines for the treatment and prevention of CVD note the role of biological markers as a fairly simple and powerful tool for diagnosing, stratifying risk and predicting CHF. However, it is unclear whether all of these biological markers are equally capable of predicting cardiovascular mortality and heart failure related outcomes in patients with acute and chronic heart failure, as well as in different phenotypes of heart failure. However, the results of numerous studies demonstrate scientific interest in the processes of angiogenesis among patients with CHF. There is an impressive body of evidence linking CHF to the level of markers such as vascular endothelial growth factor, pentraxin-3, and transforming growth factor beta. The review presents the data of domestic and foreign clinical studies devoted to the study of the level of angiogenesis markers among patients with CHF.

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