scholarly journals Dexamethasone enhances SOX9 expression in chondrocytes

2001 ◽  
Vol 169 (3) ◽  
pp. 573-579 ◽  
Author(s):  
I Sekiya ◽  
P Koopman ◽  
K Tsuji ◽  
S Mertin ◽  
V Harley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Consensus Sequence ◽  
Chondrocyte Differentiation ◽  
Sox9 Expression ◽  
Newborn Mice ◽  
Col2a1 Gene ◽  
Dose Dependent ◽  
Sox9 Protein

SOX9 is a transcription factor that activates type II procollagen (Col2a1) gene expression during chondrocyte differentiation. Glucocorticoids are also known to promote chondrocyte differentiation via unknown molecular mechanisms. We therefore investigated the effects of a synthetic glucocorticoid, dexamethasone (DEX), on Sox9 gene expression in chondrocytes prepared from rib cartilage of newborn mice. Sox9 mRNA was expressed at high levels in these chondrocytes. Treatment with DEX enhanced Sox9 mRNA expression within 24 h and this effect was observed at least up to 48 h. The effect of DEX was dose dependent, starting at 0.1 nM and maximal at 10 nM. The half life of Sox9 mRNA was approximately 45 min in the presence or absence of DEX. Western blot analysis revealed that DEX also enhanced the levels of SOX9 protein expression. Treatment with DEX enhanced Col2a1 mRNA expression in these chondrocytes and furthermore, DEX enhanced the activity of Col2-CAT (chloramphenicol acetyltransferase) construct containing a 1.6 kb intron fragment where chondrocyte-specific Sry/Sox- consensus sequence is located. The enhancing effect of DEX was specific to SOX9, as DEX did not alter the levels of Sox6 mRNA expression. These data suggest that DEX promotes chondrocyte differentiation through enhancement of SOX9.

LDL stimulates collagen mRNA synthesis in mesangial cells through induction of PKC and TGF-β expression

1999 ◽  
Vol 277 (3) ◽  
pp. F369-F376 ◽  
Author(s):  
Hyun Soon Lee ◽  
Bong Cho Kim ◽  
Hye Kyung Hong ◽  
Young Sook Kim
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Density Lipoprotein ◽  
Collagen Gene ◽  
Collagen Mrna ◽  
Collagen Gene Expression

Abnormal lipid accumulation in glomeruli could be implicated in the pathogenesis of glomerulosclerosis. Low-density lipoprotein (LDL) stimulates collagen mRNA expression in cultured human mesangial cells (HMC). To explore the possible molecular mechanisms by which LDL promotes collagen gene expression, we examined the effects of LDL on protein kinase C (PKC) activity and transforming growth factor-β (TGF-β) expression in relation to collagen gene regulation in HMC. LDL (200 μg/ml) induced an acute increase in PKC activity, particularly PKC-α and -δ, within 15 min, which decreased to control value at 2 h. LDL stimulated TGF-β1, and α1(I) and α1(IV) collagen mRNA expression within 30 min of incubation with HMC, and levels remained elevated until hour 4. LDL induced the secretion of TGF-β by HMC. This TGF-β was shown by CCL-64 mink lung cell assay to be, in part, bioactive. The stimulatory effects of LDL on collagen gene regulation in HMC were blocked by the inhibition of PKC using GF-109203X (GFX) or the downregulation of PKC using phorbol myristate acetate. Neutralizing antibody to TGF-β inhibited the increased collagen mRNA expression by HMC exposed to LDL. The downregulation or inhibition of PKC did not affect the stimulatory effect of LDL on TGF-β mRNA or protein expression. These results suggest that in HMC, LDL stimulates collagen mRNA expression through the rapid activation of PKC-α and -δ and transcriptional upregulation of TGF-β. Thus PKC and TGF-β may function as independent key signaling intermediaries in the pathway by which LDL upregulates collagen gene expression in HMC.

scholarly journals Polyphenol-Rich Extract from Propolis Reduces the Expression and Activity ofStreptococcus mutansGlucosyltransferases at Subinhibitory Concentrations

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jorge Jesús Veloz ◽  
Nicolás Saavedra ◽  
Marysol Alvear ◽  
Tomás Zambrano ◽  
Leticia Barrientos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Infectious Disease ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
Tooth Decay ◽  
Dependent Effect ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Expression And Activity

Tooth decay is an infectious disease, whose main causative agent identified isStreptococcus mutans(S. mutans). Diverse treatments have been used to eradicate this microorganism, including propolis. To date, it has been shown that polyphenols from Chilean propolis inhibitS. mutansgrowth and biofilm formation. However, the molecular mechanisms underlying this process are unclear. In the present study, we assessed the effect of Chilean propolis on the expression and activity of the glycosyltransferases enzymes and their related genes. Polyphenol-rich extract from propolis inhibited gene expression of glycosyltransferases (GtfB, GtfC, and GtfD) and their related regulatory genes, for example,VicK,VicR, andCcpA. Moreover, the treatment inhibited glucosyltransferases activity measured by the formation of sucrose-derived glucans. Additionally, an inhibitory effect was observed in the expression of SpaP involved in sucrose-independent virulence ofS. mutans. In summary, our results suggest that Chilean propolis has a dose-dependent effect on the inhibition of genes involved inS. mutansvirulence and adherence through the inhibition of glucosyltransferases, showing an anticariogenic potential of polyphenols from propolis beyondS. mutansgrowth inhibition.

scholarly journals Changes in Gene Expression during Pituitary Morphogenesis and Organogenesis in the Chick Embryo

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 989-1000 ◽  
Author(s):  
Monika Proszkowiec-Weglarz ◽  
Stacy E. Higgins ◽  
Tom E. Porter
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Anterior Pituitary ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Pituitary Development ◽  
Excellent Model ◽  
Functional Development

The anterior pituitary gland plays an important role in the regulation of many physiological processes. Formation of Rathke's pouch (RP), the precursor of the anterior pituitary, involves evagination of the oral ectoderm in a multi-step process regulated by cell interactions, signaling pathways, and transcription factors. Chickens are an excellent model to study development because of the availability of large sample sizes, accurate timing of development, and embryo accessibility. The aim of this study was to quantify mRNA expression patterns in the developing chicken anterior pituitary to evaluate the chicken embryo as a model for mammalian pituitary development. The expression profiles of 16 genes differentially expressed in RP and neuroectoderm were determined in this study. Among these, Pitx1, Pitx2, and Hesx1 mRNA levels were high on embryonic days (e) 2.5 to e3 in RP and decreased during development. Expression of Pit1 and Tbx19 mRNA in RP reached the highest levels by e7 and e6.5, respectively. Levels of glycoprotein subunit α mRNA increased beginning at e4. FGF8 mRNA showed the highest expression at e3 to e3.5 in neuroectoderm. BMP2 showed slight decreases in mRNA expression in both tissues during development, while Isl1 and Noggin mRNA expression increased in later development. Taken together, we present the first quantitative transcriptional profile of pituitary organogenesis. Our results will help further understanding of the functional development of this gland. Moreover, because of the high similarity in gene expression patterns observed between chicken and mouse, chickens could serve as an excellent model to study genetic and molecular mechanisms underlying pituitary development.

Ferrum phosphoricum D12 Treatment Affects J774A.1 Cell Proliferation, Transcription Levels of Iron Metabolism, Antioxidant Defense, and Inflammation-related Genes

Homeopathy ◽  
2021 ◽  
Author(s):  
Oskan Tasinov ◽  
Yoana Kiselova-Kaneva ◽  
Desislava Ivanova ◽  
Milena Pasheva ◽  
Deyana Vankova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Mrna Expression ◽  
Iron Metabolism ◽  
Antioxidant Defense ◽  
Molecular Mechanisms ◽  
Expression Levels ◽  
Significant Stimulation ◽  
Element Binding Protein ◽  
Responsive Element

Abstract Background Ferrum phosphoricum (FP) is prescribed as a homeopathic remedy to treat the early stages of fever and inflammation in cases of colds or flu, muscle fatigue and anemia. We aimed to analyze the molecular mechanisms of action of FP D12 on cell proliferation and mRNA expression of iron metabolism, antioxidant defense and inflammation-related genes in mouse J774A.1 macrophages. Methods Cell proliferation was examined using the MTT test. RT-qPCR analyses were performed to estimate gene expression changes. Relative gene expression levels were calculated using the 2–ΔΔCt method. The effect of treatment using FP D12 tablets was compared with that using placebo tablets (PT). Results FP D12 in low concentrations (0.0125 mg/mL to 0.025 mg/mL) significantly stimulated proliferation of J774A.1 cells by up to 11% (p < 0.01) versus control untreated cells and by up to 40% (p < 0.01) versus PT-treated cells in the respective concentration. FP D12 versus PT induced a significant increase in mRNA expression of ferritin light chain (Ftl1) (by 8-fold, p < 0.01), β-2-microglobulin (B2m) (by 2.5-fold, p < 0.05) and iron-responsive element binding protein 2 (Ireb2) (by 4-fold, p < 0.05), and induced a slight decrease in myosin IE (Myo1e) mRNA expression levels (by 0.4-fold, p < 0.01) in macrophages. A highly significant (r2 = 0.99, p < 0.05) correlation was observed between Ireb2 and B2m transcription levels. Significant stimulation of antioxidant enzyme Gpx-1 (by 1.27-fold, p < 0.01) in cells by 0.025 mg/mL FP D12, but a slight decrease (by 0.12-fold, p < 0.05) in 0.0125 mg/mL-treated cells, was observed. A significant increase in the gene expression of IL-1β (by 3.5-fold, р < 0.05) in macrophages was also detected. Conclusion Ferrum phosphoricum in D12 dilution potentially exhibits iron retention, antioxidant and immunomodulation activities, possibly by modulating transcription levels of related genes in non-stimulated mouse macrophages.

Momordica charantia Inhibits Inflammatory Responses in Murine Macrophages via Suppression of TAK1

2018 ◽  
Vol 46 (02) ◽  
pp. 435-452 ◽  
Author(s):  
Woo Seok Yang ◽  
Eunju Yang ◽  
Min-Jeong Kim ◽  
Deok Jeong ◽  
Deok Hyo Yoon ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Momordica Charantia ◽  
Luciferase Reporter ◽  
No Production ◽  
Dependent Manner ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Dose Dependent

Momordica charantia known as bitter melon is a representative medicinal plant reported to exhibit numerous pharmacological activities such as antibacterial, antidiabetic, anti-inflammatory, anti-oxidant, antitumor, and hypoglycemic actions. Although this plant has high ethnopharmacological value for treating inflammatory diseases, the molecular mechanisms by which it inhibits the inflammatory response are not fully understood. In this study, we aim to identify the anti-inflammatory mechanism of this plant. To this end, we studied the effects of its methanol extract (Mc-ME) on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Specifically, we evaluated nitric oxide (NO) production, mRNA expression of inflammatory genes, luciferase reporter gene activity, and putative molecular targets. Mc-ME blocked NO production in a dose-dependent manner in RAW264.7 cells; importantly, no cytotoxicity was observed. Moreover, the mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by Mc-ME treatment in a dose-dependent manner. Luciferase assays and nuclear lysate immunoblotting analyses strongly indicated that Mc-ME decreases the levels of p65 [a nuclear factor (NF)-[Formula: see text]B subunit] and c-Fos [an activator protein (AP)-1 subunit]. Whole lysate immunoblotting assays, luciferase assays, and overexpression experiments suggested that transforming growth factor [Formula: see text]-activated kinase 1 (TAK1) is targeted by Mc-ME, thereby suppressing NF-[Formula: see text]B and AP-1 activity via downregulation of extracellular signal-regulated kinases (ERKs) and AKT. These results strongly suggest that Mc-ME exerts its anti-inflammatory activity by reducing the action of TAK1, which also affects the activation of NF-[Formula: see text]B and AP-1.

scholarly journals Unraveling reno-protective effects of SGLT2 inhibition in human proximal tubular cells

2019 ◽  
Vol 316 (3) ◽  
pp. F449-F462 ◽  
Author(s):  
Markus Pirklbauer ◽  
Ramona Schupart ◽  
Lisa Fuchs ◽  
Petra Staudinger ◽  
Ulrike Corazza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Mrna Level ◽  
Pathway Enrichment Analysis ◽  
Protective Effects ◽  
Proximal Tubular ◽  
Pt Cell ◽  
Tgf Β1

Large clinical trials demonstrated that SGLT2 inhibitors (SGLT2i) slow the progression of kidney function decline in type 2 diabetes. Because the underlying molecular mechanisms are largely unknown, we studied the effects of SGLT2i on gene expression in two human proximal tubular (PT) cell lines under normoglycemic conditions, utilizing two SGLT2i, namely empagliflocin and canagliflocin. Genome-wide expression analysis did not reveal substantial differences between these two SGLT2i. Microarray hybridization analysis identified 94 genes that were both upregulated by TGF-β1 and downregulated by either of the two SGLT2i in HK-2 and RPTEC/TERT1 (renal proximal tubular epithelial cells/telomerase reverse transcriptase 1) cells. Extracellular matrix organization showed the highest significance in pathway enrichment analysis. Differential gene expression of three annotated genes of interest within this pathway was verified on mRNA level in both cell lines. Whereas TGF-β1 induced mRNA expression of thrombospondin 1 (THBS1; 4.3-fold), tenascin C (TNC; 8-fold), and platelet-derived growth factor subunit B (PDGF-B; 4.2-fold), SGLT2i downregulated basal mRNA expression of THBS1 (0.2-fold), TNC (0.5 fold), and PDGF-B (0.6-fold). Administration of SGLT2i in the presence of TGF-β1 resulted in a significant inhibition of TGF-β1-induced THBS1 and TNC mRNA expression and TGF-β1-induced THBS1, TNC, and PDGF-BB protein expression. We conclude that SGLT2i block basal and TGF-β1-induced expression of key mediators of renal fibrosis and kidney disease progression in two independent human PT cell lines.

scholarly journals Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription

2011 ◽  
Vol 22 (8) ◽  
pp. 1300-1311 ◽  
Author(s):  
Katsuhiko Amano ◽  
Kenji Hata ◽  
Shuji Muramatsu ◽  
Makoto Wakabayashi ◽  
Yoko Takigawa ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Gene Promoter ◽  
Transcriptional Regulators ◽  
Chondrocyte Differentiation ◽  
Col2a1 Gene ◽  
Organ Culture System ◽  
Histone 3 ◽  
Col2a1 Expression ◽  
Essential Transcription Factor

SRY-box–containing gene 9 (Sox9) is an essential transcription factor in chondrocyte lineage determination and differentiation. Recent studies demonstrated that Sox9 controls the transcription of chondrocyte-specific genes in association with several other transcriptional regulators. To further understand the molecular mechanisms by which Sox9 influences transcriptional events during chondrocyte differentiation, we attempted to identify transcriptional partners of Sox9 and to examine their roles in chondrocyte differentiation. We isolated AT-rich interactive domain–containing protein 5a (Arid5a; also known as Mrf1) as an activator of the Col2a1 gene promoter from an ATDC5 cDNA library. Arid5a was highly expressed in cartilage and induced during chondrocyte differentiation. Furthermore, Arid5a physically interacted with Sox9 in nuclei and up-regulated the chondrocyte-specific action of Sox9. Overexpression of Arid5a stimulated chondrocyte differentiation in vitro and in an organ culture system. In contrast, Arid5a knockdown inhibited Col2a1 expression in chondrocytes. In addition, Arid5a binds directly to the promoter region of the Col2a1 gene and stimulates acetylation of histone 3 in the region. Our results suggest that Arid5a may directly interact with Sox9 and thereby enhance its chondrocyte-specific action.

scholarly journals Cytokine-mediated regulation of expression of Gfi1 and U2afll4 genes activated by T-cells with different differentiation status in vitro

2016 ◽  
Vol 62 (2) ◽  
pp. 180-186
Author(s):  
K.A. Yurova ◽  
N.A. Sokhonevich ◽  
O.G. Khaziakhmatova ◽  
L.S. Litvinova
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Molecular Mechanisms ◽  
Splice Variants ◽  
Inhibitory Effect ◽  
Regulation Of Expression ◽  
Dose Dependent Decrease ◽  
Differentiation Status ◽  
Dose Dependent

The dose-dependent effects of cytokines (IL-2, IL-7, and IL-15), which have a common g-chain, on mRNA expression of U2afll4 and GFi1 genes involved in regulation of alternative splicing of the Ptprc gene, have been investigated in vitro using T-lymphocyte cultures with different degrees of differentiation. IL-2, IL-7, and IL-15 caused a similar unidirectional inhibitory effect of various severity on restimulated CD45RO+ T-cells exposed to an antigen-independent activation; they caused a dose-dependent decrease of the U2af1l4 gene expression, and an increase of Gfi1 gene expression. This may suggest formation of active forms of the CD45 receptor, and also limitation of the formation of low-molecular short splice variants of the CD45RO receptor. Under conditions of antigen-independent stimulation of naive CD45RA+-cells rIL-7 and IL-15 exhibited opposite effects on U2af1l4 and Gfi1 gene expression. The increase of IL-7 concentrations in the incubation medium of naive cells was accompanied by a decrease in expression of both genes. IL-15 IL-7 exhibited opposite effects. Cytokines possessing a common g-chain (IL-2, IL-7, and IL-15) prevented antigen-independent differentiation of naive T-cells, by preventing the formation of polyclonal “surrogate“ cells. In general, the study of the molecular mechanisms of genetic control determining homeostatic processes of T-cells in response to exposure to antigenic or non-antigenic treatments may be important for construction of a general model of self-maintenance and differentiation of immune cells

Interferon-γ suppresses activin A/NF-E2 induction of erythroid gene expression through the NF-κB/c-Jun pathway

2014 ◽  
Vol 306 (4) ◽  
pp. C407-C414 ◽  
Author(s):  
Wei-Hwa Lee ◽  
Ming-Hui Chung ◽  
Yu-Hui Tsai ◽  
Ju-Ling Chang ◽  
Huei-Mei Huang
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Luciferase Activity ◽  
Globin Gene ◽  
Activin A ◽  
Dependent Manner ◽  
Promoter Activation ◽  
Ifn Γ ◽  
Globin Promoter ◽  
Dose Dependent

Interferon (IFN)-γ is a proinflammatory cytokine that is linked to erythropoiesis inhibition and may contribute to anemia. However, the mechanism of IFN-γ-inhibited erythropoiesis is unknown. Activin A, a member of the transforming growth factor (TGF)-β superfamily, induces the erythropoiesis of hematopoietic progenitor cells. In this study, a luciferase reporter assay showed that IFN-γ suppressed activin A-induced ζ-globin promoter activation in K562 erythroblast cells in a dose-dependent manner. Activin A reversed the suppressive effect of IFN-γ on the luciferase activity of ζ-globin promoter in a dose-dependent manner. IFN-γ also suppressed the activation of activin A-induced α-globin promoter. IFN-γ reduced the mRNA expression of α-globin, ζ-globin, NF-E2p45, and GATA-1 induced by activin A. The results also showed that IFN-γ induced c-Jun expression when NF-κBp65 and c-Jun bound to two AP-1-binding sites on the c-Jun promoter. The luciferase activity of α-globin and ζ-globin promoters were enhanced by wild-type c-Jun and eliminated by dominant-negative (DN) c-Jun. The suppressive effects of IFN-γ on the mRNA expression of α-globin and ζ-globin were absent in cells expressing DN c-Jun. The ability of NF-E2 to enhance activin A-induced ζ-globin promoter activation decreased when c-Jun was present, and IFN-γ treatment further enhanced the decreasing effect of c-Jun. Chromatin immunoprecipitation revealed that NF-E2p45 bound to the upstream regulatory element (HS-40) of the α-globin gene cluster in response to activin A, whereas c-Jun eliminated this binding. These results suggest that IFN-γ modulates NF-κB/c-Jun to antagonize activin A-mediated NF-E2 transcriptional activity on globin gene expression.

scholarly journals The Effect of Continuous Light on Growth and Muscle-Specific Gene Expression in Atlantic Salmon (Salmo salar L.) Yearlings

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 328
Author(s):  
Natalia S. Shulgina ◽  
Maria V. Churova ◽  
Svetlana A. Murzina ◽  
Marina Yu. Krupnova ◽  
Nina N. Nemova
Keyword(s):  
Gene Expression ◽  
Atlantic Salmon ◽  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Muscle Growth ◽  
Somatic Growth ◽  
Continuous Light ◽  
Specific Gene ◽  
Mrna Levels ◽  
Expression Levels

Photoperiod is associated to phenotypic plasticity of somatic growth in several teleost species, however, the molecular mechanisms underlying this phenomenon are currently unknown. The effect of a continuous lighting (LD 24:0), compared with the usual hatchery lighting (HL) regime, on the growth rate and gene expression of myogenic regulatory factors (MRFs: MyoD1 paralogs, Myf5, and MyoG) myosin heavy chain (MyHC), and MSTN paralogs in the white muscles of hatchery-reared Atlantic salmon yearlings was evaluated over a 6-month period (May to October). The levels of gene expression were determined using real-time PCR. Continuous lighting was shown to have a positive effect on weight gain. MyHC, MyoD1c, MyoD1b, and MSTN1a/b mRNA expression was influenced by the light regime applied. In all the studied groups, a significant positive correlation was observed between the expression levels of MRFs and MSTN paralogs throughout the experiment. The study demonstrated seasonal patterns regarding the simultaneous expression of several MRFs. MyoD1a, MyoG, and MyHC mRNA expression levels were elevated in the mid-October, but MyoD1b/c, and Myf5 mRNA levels decreased by the end of this month. In general, the findings showed that constant lighting affected the regulatory mechanisms of muscle growth processes in salmon.

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