Decorin promotes apoptosis and autophagy via suppressing c-Met in HTR-8 trophoblasts

Decorin (DCN) regulates a vast array of cellular processes including proliferation, migration, apoptosis, and autophagy, and its aberrant expression has been associated with poor extravillous trophoblasts (EVT) invasion of the uterus, which underlies the occurrence of preeclampsia (PE) and intrauterine growth restriction (IUGR). In this study, we aim to elucidate the molecular mechanism of how the DCN regulates the cell functions through the use of trophoblast cell line, HTR-8. Using a series of cell function assays, including CCK8, RTCA, transwell, scratch-wound assay, and Annexin V staining, we found that DCN suppressed proliferation and invasion, while promoted autophagy and apoptosis of HTR-8 in a dose-dependent manner. Transient stimulation of DCN have increased the activity of c-Met and its downstream effectors – Akt, FAK and m-TOR. However, a prolonged exposure to DCN have significantly downregulated the expression of c-Met, leading to suppression of its downstream effectors. Lentivirus that overexpressed c-Met targeting shRNA was used to knockdown c-Met expression and crizotinib was used to selectively inhibit the kinase activity of c-Met in HTR-8 cells. A combination of DCN and c-Met knockdown/inhibition have reduced the proliferation and invasion in HTR-8 cells; however, DCN-induced autophagy and apoptosis were not synergistically enhanced by c-Met inhibition. In conclusion, DCN promotes autophagy and apoptosis predominantly through downregulating c-Met/Akt/mTOR activity in human trophoblasts.

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Glucose Triggers ATP Secretion from Bacteria in a Growth-Phase-Dependent Manner

Applied and Environmental Microbiology ◽

10.1128/aem.03871-12 ◽

2013 ◽

Vol 79 (7) ◽

pp. 2328-2335 ◽

Cited By ~ 36

Author(s):

Ippei Hironaka ◽

Tadayuki Iwase ◽

Shinya Sugimoto ◽

Ken-ichi Okuda ◽

Akiko Tajima ◽

...

Keyword(s):

Stationary Phase ◽

Growth Phase ◽

Cell Function ◽

Immune Cell ◽

Dependent Manner ◽

T Helper 17 ◽

Content Type ◽

Cell Functions ◽

Atp Secretion ◽

Enterococcus Gallinarum

ABSTRACTATP modulates immune cell functions, and ATP derived from gut commensal bacteria promotes the differentiation of T helper 17 (Th17) cells in the intestinal lamina propria. We recently reported thatEnterococcus gallinarum, isolated from mice and humans, secretes ATP. We have since found and characterized several ATP-secreting bacteria. Of the tested enterococci,Enterococcus mundtiisecreted the greatest amount of ATP (>2 μM/108cells) after overnight culture. Glucose, not amino acids and vitamins, was essential for ATP secretion fromE. mundtii. Analyses of energy-deprived cells demonstrated that glycolysis is the most important pathway for bacterial ATP secretion. Furthermore, exponential-phaseE. mundtiiandEnterococcus faecaliscells secrete ATP more efficiently than stationary-phase cells. Other bacteria, includingPseudomonas aeruginosa,Escherichia coli, andStaphylococcus aureus, also secrete ATP in exponential but not stationary phase. These results suggest that various gut bacteria, including commensals and pathogens, might secrete ATP at any growth phase and modulate immune cell function.

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Responses of primary osteoblasts and osteoclasts from hemizygous β-globin knockout thalassemic mice with elevated plasma glucose to 1,25-dihydroxyvitamin D3

Scientific Reports ◽

10.1038/s41598-019-50414-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Narattaphol Charoenphandhu ◽

Ratchaneevan Aeimlapa ◽

Supagarn Sooksawanwit ◽

Jirawan Thongbunchoo ◽

Jarinthorn Teerapornpuntakit ◽

...

Keyword(s):

Bone Loss ◽

Prolonged Exposure ◽

Cell Function ◽

Calcium Absorption ◽

Bone Cells ◽

Cathepsin K ◽

Bone Cell ◽

Aberrant Expression ◽

High Blood Glucose ◽

Extracellular Glucose

Abstract β-thalassemia is often associated with hyperglycemia, osteoporosis and increased fracture risk. However, the underlying mechanisms of the thalassemia-associated bone loss remain unclear. It might result from abnormal activities of osteoblasts and osteoclasts, and perhaps prolonged exposure to high extracellular glucose. Herein, we determined the rate of duodenal calcium transport in hemizygous β-globin knockout thalassemic (BKO) mice. Their bones were collected for primary osteoblast and osteoclast culture. We found that BKO mice had lower calcium absorption than their wild-type (WT) littermates. Osteoblasts from BKO mice showed aberrant expression of osteoblast-specific genes, e.g., Runx2, alkaline phosphatase and osteocalcin, which could be partially restored by 1,25(OH)2D3 treatment. However, the mRNA expression levels of RANK, calcitonin receptor (Calcr), c-Fos, NFATc1, cathepsin K and DMT1 were similar in both BKO and WT groups. Exposure to high extracellular glucose modestly but significantly affected the expression of osteoclast-specific markers in WT osteoclasts with no significant effect on osteoblast-specific genes in WT osteoblasts. Thus, high glucose alone was unable to convert WT bone cells to BKO-like bone cells. In conclusion, the impaired calcium absorption and mutation-related aberrant bone cell function rather than exposure to high blood glucose were likely to be the principal causes of thalassemic bone loss.

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MiR-148b, MiR-152/ALCAM Axis Regulates the Proliferation and Invasion of Pituitary Adenomas Cells

Cellular Physiology and Biochemistry ◽

10.1159/000485342 ◽

2017 ◽

Vol 44 (2) ◽

pp. 792-803 ◽

Cited By ~ 13

Author(s):

Wei He ◽

Ling Huang ◽

Min Li ◽

Yue Yang ◽

Zhen Chen ◽

...

Keyword(s):

Pituitary Adenomas ◽

Target Genes ◽

Annexin V ◽

Expression Level ◽

Human Pituitary ◽

Aberrant Expression ◽

Leukocyte Antigen ◽

Noninvasive Samples ◽

Proliferation And Invasion

Background/Aims: Aberrant expression of miRNA has been found in many tumor tissues to regulate the tumorigenesis by binding to the 3`- untranslated region (3`-UTR) of the target genes. The aim of this study is to investigate the role of miR-148b, miR-152/ALCAM axis in human pituitary adenomas (PAs). Methods: First, we detected the expression level of miR-148b-3p and miR-152 in human PAs samples by using qRT-PCR. Then we studied the role of miR-148b-3p, miR-152 on human PAs cell proliferation, invasion and apoptosis by using MTS assay, Transwell invasion assay and Annexin V/PI Staining Test. To study the relationship between miR-148b-3p, miR-152 and activated leukocyte antigen molecule (ALCAM), we overexpressed miR-148-3p or miR-152 by transfecting specific mimics. Lucifearase reporter assay was then performed to confirm the target. Next, we studied the biological functions of ALCAM in human PAs cells. Finally, the role of miR-148b-3p, miR-152/ALCAM axis in PAs cells was studied. Results: The expression level of miR-148-3p and miR-152 in invasive PAs samples was lower than those in noninvasive samples. Overexpression of miR-148b-3p, miR-152 could repress proliferation and invasion, and promote apoptosis. Moreover, miR-148b-3p and miR-152 could repress activated leukocyte antigen molecule (ALCAM) expression. Knockdown of ALCAM could repress proliferation and invasion and promote apoptosis. By contrary, overexpression of ALCAM promoted proliferation and invasion. Further, the rescue experiments indicated that overexpression of ALCAM significantly restored the proliferation, apoptosis, and invasion influenced by miR-148b-3p and miR-152. Conclusions: Our study suggests that miR-148b-3p, miR-152 may serve as suppressors in PAs through downregulating ALCAM expression. miR-148b, miR-152/ ALCAM axis may be a new therapeutic target in the future.

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The F11 Receptor (F11R)/Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A) in cancer progression

Molecular and Cellular Biochemistry ◽

10.1007/s11010-021-04259-2 ◽

2021 ◽

Author(s):

Kamila Czubak-Prowizor ◽

Anna Babinska ◽

Maria Swiatkowska

Keyword(s):

Cancer Progression ◽

Adhesion Molecule ◽

Epithelial To Mesenchymal Transition ◽

Cell Function ◽

Immunoglobulin Superfamily ◽

Dependent Manner ◽

Aberrant Expression ◽

Mesenchymal Transition ◽

Transmembrane Glycoprotein ◽

Tight Junction Formation

AbstractThe F11 Receptor (F11R), also called Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A), is a transmembrane glycoprotein of the immunoglobulin superfamily, which is mainly located in epithelial and endothelial cell tight junctions and also expressed on circulating platelets and leukocytes. It participates in the regulation of various biological processes, as diverse as paracellular permeability, tight junction formation and maintenance, leukocyte transendothelial migration, epithelial-to-mesenchymal transition, angiogenesis, reovirus binding, and platelet activation. Dysregulation of F11R/JAM-A may result in pathological consequences and disorders in normal cell function. A growing body of evidence points to its role in carcinogenesis and invasiveness, but its tissue-specific pro- or anti-tumorigenic role remains a debated issue. The following review focuses on the F11R/JAM-A tissue-dependent manner in tumorigenesis and metastasis and also discusses the correlation between poor patient clinical outcomes and its aberrant expression. In the future, it will be required to clarify the signaling pathways that are activated or suppressed via the F11R/JAM-A protein in various cancer types to understand its multiple roles in cancer progression and further use it as a novel direct target for cancer treatment.

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A flexible ontology for inference of emergent whole cell function from relationships between subcellular processes

10.1101/112201 ◽

2017 ◽

Author(s):

Jens Hansen ◽

David Meretzky ◽

Simeneh Woldesenbet ◽

Gustavo Stolovitzky ◽

Ravi Iyengar

Keyword(s):

Cell Biology ◽

Cell Function ◽

Biological Knowledge ◽

Dependent Manner ◽

Whole Cell ◽

Cell Functions ◽

Cell Responses ◽

Growing Cell ◽

Cell Ontology ◽

Context Specific

AbstractWhole cell responses arise from coordinated interactions between diverse human gene products functioning within various pathways underlying sub-cellular processes (SCP). Lower level SCPs interact to form higher level SCPs, often in a context specific manner to give rise to whole cell function. We sought to determine if capturing such relationships enables us to describe the emergence of whole cell functions from interacting SCPs. We developed the “Molecular Biology of the Cell” ontology based on standard cell biology and biochemistry textbooks and review articles. Currently, our ontology contains 5,385 genes, 753 SCPs and 19,180 expertly curated gene-SCP associations. Our algorithm to populate the SCPs with genes enables extension of the ontology on demand and the adaption of the ontology to the continuously growing cell biological knowledge. Since whole cell responses most often arise from the coordinated activity of multiple SCPs, we developed a dynamic enrichment algorithm that flexibly predicts SCP-SCP relationships beyond the current taxonomy. This algorithm enables us to identify interactions between SCPs as a basis for higher order function in a context dependent manner, allowing us to provide a detailed description of how SCPs together can give rise to whole cell functions. We conclude that this ontology can, from omics data sets, enable the development of detailed multidimensional SCP networks for predictive modeling of emergent whole cell functions.

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Up-Regulation of GATA4 Regulates Human Lens Epithelial Cell Function in Age-Related Cataract

Ophthalmic Research ◽

10.1159/000507962 ◽

2020 ◽

Vol 63 (6) ◽

pp. 564-571

Author(s):

Xiaodong Xie ◽

Xiaofei Song ◽

Xin Liu ◽

Xiaogang Luo ◽

Maidina Nabijiang ◽

...

Keyword(s):

Prolonged Exposure ◽

Cell Function ◽

Critical Role ◽

Lens Epithelial Cell ◽

Human Lens ◽

Dependent Manner ◽

Age Related

Purpose: GATA4 has emerged as a novel regulator that plays a critical role in mediating senescence. However, the role of GATA4 in age-related cataract (ARC), the leading cause of visual impairment, requires further elucidation. Methods: GATA4 expression was measured by quantitative RT-PCR and capillary Western immunoassay (WES). The MTT assay, EdU assay, and rhodamine-123/Hoechst and calcein-AM/propidium iodide double staining were used to investigate the role of GATA4 in the viability, proliferation, and apoptosis of cultured human lens epithelial cells (HLECs). Results: HLECs were subjected to 3 different treatment models, including prolonged exposure to low-dose H2O2, UVB irradiation, and mild heating, to simulate senescence and apoptosis. GATA4 expression was significantly increased in these models in a time- and dose-dependent manner. Overexpression of GATA4 reduced cell viability, accelerated apoptosis development, and reduced the proliferation of HLECs. Furthermore, the expression of GATA4 from ARC was up-regulated at both mRNA and at protein level compared with clear lenses. Conclusion: GATA4 is up-regulated in all 3 models of HLECs in vitro and the cells from ARC lenses in vivo. Up-regulation of GATA4 mediates HLEC dysfunction. GATA4-mediated effects in HLECs would provide a novel insight into the pathogenesis of ARC.

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Shikonin Inhibits Cholangiocarcinoma Cell Line QBC939 by Regulating Apoptosis, Proliferation, and Invasion

Cell Transplantation ◽

10.1177/0963689720979162 ◽

2021 ◽

Vol 30 ◽

pp. 096368972097916

Author(s):

Chang Liu ◽

Li-Qian Xuan ◽

Kai Li ◽

Zhuo Feng ◽

Chan Lv ◽

...

Keyword(s):

Caspase 3 ◽

Growth Factor Receptor ◽

Annexin V ◽

Caspase 8 ◽

Dependent Manner ◽

Invasion Assay ◽

Egfr Expression ◽

Transwell Invasion Assay ◽

Induced Apoptosis ◽

Proliferation And Invasion

This study was designed to clarify whether Shikonin causes proliferation, apoptosis, and invasion in cholangiocarcinoma cells and to investigate the mechanism of action. QBC939 cells were cultured with different doses of Shikonin, and then 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium assay was used to detect cell viability. Apoptosis of cells was detected using flow cytometry with Annexin V/propidium iodide (PI) assay after being stained with Hoechst 33242. The role of Shikonin on the invasive and metastasis ability was detected using Transwell invasion assay. Real-time polymerase chain reaction and Western blotting were used to detect the expression of caspase-3, caspase-8, epidermal growth factor receptor (EGFR), and matrix metalloproteinase (MMP)-9. Shikonin inhibited proliferation and invasive ability of QBC939 cells in a dose-dependent manner; at the same time, apoptosis of cells was also observed in a concentration-dependent fashion. Moreover, Annexin V/PI assay and Transwell invasion assay results indicated that Shikonin induced apoptosis and invasion inhibitory probably due to upregulation of caspase-3 and caspase-8 expression and downregulation of MMP-9 and EGFR expression in a concentration-dependent fashion. Shikonin could enhance apoptosis and inhibit proliferation and invasion of QBC939 cells; such biological behaviors mainly occurred via upregulating the expression of caspase-3 and caspase-8 and downregulating the expression of MMP-9 and EGFR.

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A New Take on Prion Protein Dynamics in Cellular Trafficking

International Journal of Molecular Sciences ◽

10.3390/ijms21207763 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7763

Author(s):

Rodrigo Nunes Alves ◽

Rebeca Piatniczka Iglesia ◽

Mariana Brandão Prado ◽

Maria Isabel Melo Escobar ◽

Jacqueline Marcia Boccacino ◽

...

Keyword(s):

Prion Protein ◽

Cell Function ◽

Cellular Prion Protein ◽

Specific Cell ◽

Membrane Domains ◽

Cellular Processes ◽

Cell Functions ◽

Heterogeneous Membrane ◽

Cell Compartments ◽

Distinct Cell

The mobility of cellular prion protein (PrPC) in specific cell membrane domains and among distinct cell compartments dictates its molecular interactions and directs its cell function. PrPC works in concert with several partners to organize signaling platforms implicated in various cellular processes. The scaffold property of PrPC is able to gather a molecular repertoire to create heterogeneous membrane domains that favor endocytic events. Dynamic trafficking of PrPC through multiple pathways, in a well-orchestrated mechanism of intra and extracellular vesicular transport, defines its functional plasticity, and also assists the conversion and spreading of its infectious isoform associated with neurodegenerative diseases. In this review, we highlight how PrPC traffics across intra- and extracellular compartments and the consequences of this dynamic transport in governing cell functions and contributing to prion disease pathogenesis.

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Active Compound of Pharbitis Semen (Pharbitis nil Seeds) Suppressed KRAS-Driven Colorectal Cancer and Restored Muscle Cell Function during Cancer Progression

Molecules ◽

10.3390/molecules25122864 ◽

2020 ◽

Vol 25 (12) ◽

pp. 2864 ◽

Cited By ~ 1

Author(s):

Jisu Song ◽

Heejung Seo ◽

Mi-Ryung Kim ◽

Sang-Jae Lee ◽

Sooncheol Ahn ◽

...

Keyword(s):

Colorectal Cancer ◽

Muscle Cell ◽

Cancer Progression ◽

Active Compound ◽

Cell Function ◽

Morning Glory ◽

Pharbitis Nil ◽

Dependent Manner ◽

Cell Functions ◽

Starting Point

Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer (CRC) is notorious to target with drugs and has shown ineffective treatment response. The seeds of Pharbitis nil, also known as morning glory, have been used as traditional medicine in East Asia. We focused on whether Pharbitis nil seeds have a suppressive effect on mutated KRAS-driven CRC as well as reserving muscle cell functions during CRC progression. Seeds of Pharbitis nil (Pharbitis semen) were separated by chromatography and the active compound of Pharbitis semen (PN) was purified by HPLC. The compound PN efficiently suppressed the proliferation of mutated KRAS-driven CRC cells and their clonogenic potentials in a concentration-dependent manner. It also induced apoptosis of SW480 human colon cancer cells and cell cycle arrest at the G2/M phase. The CRC related pathways, including RAS/ERK and AKT/mTOR, were assessed and PN reduced the phosphorylation of AKT and mTOR. Furthermore, PN preserved muscle cell proliferation and myotube formation in cancer conditioned media. In summary, PN significantly suppressed mutated KRAS-driven cell growth and reserved muscle cell function. Based on the current study, PN could be considered as a promising starting point for the development of a nature-derived drug against KRAS-mutated CRC progression.

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The Actin-Bundling Protein L-Plastin: A Critical Regulator of Immune Cell Function

International Journal of Cell Biology ◽

10.1155/2012/935173 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 44

Author(s):

Sharon Celeste Morley

Keyword(s):

B Lymphocyte ◽

Cell Function ◽

Immune Cell ◽

Specific Protein ◽

Cellular Processes ◽

Cell Functions ◽

Antigen Receptor Signaling ◽

Cross Links ◽

The Stability ◽

And Function

L-plastin is a leukocyte-specific protein that cross-links actin filaments into tight bundles, increasing the stability of actin-based structures such as podosomes and lamellipodia. While first identified as an abundant cytoplasmic protein in hematopoietically derived cells over 25 years ago, the requirement for L-plastin in multiple functions critical for immunity, such as antigen receptor signaling, adhesion, and motility, has only recently become clear. L-plastin has been identified as an important component in cellular processes critical for neutrophil, macrophage, osteoclast, eosinophil, and T- and B-lymphocyte biology. Following a brief description of the structure and function of L-plastin, the regulation of immune cell functions by L-plastin will be reviewed in detail.

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