scholarly journals Methanol extract of Iphiona aucheri ameliorates CCl4 induced hepatic injuries by regulation of genes in rats

2019 ◽  
Vol 8 (6) ◽  
pp. 815-832
Author(s):  
Jawaid Ahmed Zai ◽  
Muhammad Rashid Khan ◽  
Zaib un Nisa Mughal ◽  
Riffat Batool ◽  
Irum Naz ◽  
...  
Keyword(s):  
Er Stress ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Methanol Extract ◽  
Binding Protein ◽  
Control Group ◽  
Type I ◽  
Dependent Manner ◽  
Antioxidant Genes ◽  
Inflammatory Genes

Abstract We have investigated the protective potential of methanol extract of Iphiona aucheri (IAM) on the expression of endoplasmic reticulum (ER) stress associated genes and inflammatory genes on carbon tetrachloride (CCl4) induced hepatic toxicity in rats. Hepatic damage markers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin were elevated while the content of antioxidants: catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and reduced glutathione (GSH) were decreased significantly (p < 0.05) in CCl4 treated rats as compared to the control group. The CCl4 intoxication induced a higher expression of glucose-regulated protein 78 kDa (GRP78), X-box-binding protein 1 total (XBP1t), spliced X-box-binding protein 1 (XBP1s), unspliced X-box-binding protein 1 (XBP1u), C/EBP homologous protein (CHOP) and genes involved in inflammation and fibrosis: tumor necrosis factor alpha (TNF-α), transforming growth factor-beta (TGF-β), mothers against DPP homolog 3 (SMAD3), alpha skeletal muscle actin (αSMA) and collagen type I alpha 1 chain (COL1A1). The intoxicated rats showed a low expression of the glutamate–cysteine ligase catalytic subunit (GCLC), protein disulfide isomerase (PDI) and nuclear factor (erythroid-derived 2) like-2 (Nrf2). The administration of IAM to intoxicated rats restored the expression of ER stress, inflammatory, fibrosis and antioxidant genes in a dose dependent manner. Our results indicated that IAM can impede the ER stress and inflammatory genes and it could be a complementary and alternative therapeutic agent for oxidative stress associated disorders.

scholarly journals Role of the latent TGF-beta binding protein in the activation of latent TGF-beta by co-cultures of endothelial and smooth muscle cells.

1993 ◽  
Vol 120 (4) ◽  
pp. 995-1002 ◽  
Author(s):  
R Flaumenhaft ◽  
M Abe ◽  
Y Sato ◽  
K Miyazono ◽  
J Harpel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Muscle Cells ◽  
Beta Activity ◽  
Dependent Manner ◽  
Tgf Beta

Transforming growth factor beta (TGF-beta) is released from cells in a latent form consisting of the mature growth factor associated with an aminoterminal propeptide and latent TGF-beta binding protein (LTBP). The endogenous activation of latent TGF-beta has been described in co-cultures of endothelial and smooth muscle cells. However, the mechanism of this activation remains unknown. Antibodies to native platelet LTBP and to a peptide fragment of LTBP inhibit in a dose-dependent manner the activation of latent TGF-beta normally observed when endothelial cells are cocultured with smooth muscle cells. Inhibition of latent TGF-beta activation was also observed when cells were co-cultured in the presence of an excess of free LTBP. These data represent the first demonstration of a function for the LTBP in the extracellular regulation of TGF-beta activity and indicate that LTBP participates in the activation of latent TGF-beta, perhaps by concentrating the latent growth factor on the cell surface where activation occurs.

scholarly journals BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary

2005 ◽  
Vol 186 (1) ◽  
pp. 109-121 ◽  
Author(s):  
M-O Faure ◽  
L Nicol ◽  
S Fabre ◽  
J Fontaine ◽  
N Mohoric ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hormone Secretion ◽  
Inhibitory Effect ◽  
Type I ◽  
Mrna Levels ◽  
Dependent Manner

Activins and inhibins, members of the transforming growth factor-beta family are able to stimulate and inhibit, respectively, FSH synthesis and release. Other members of this superfamily, the bone morphogenetic proteins (BMPs), may also affect FSH synthesis in the mouse. The aim of this work was to determine whether BMPs are expressed in the ovine pituitary and whether they play a role in the regulation of FSH release. The mRNAs encoding BMP-2, BMP-4, BMP-7 and the oocyte-derived growth factor, growth differentiation factor (GDF)-9 were detected in the pituitaries of cyclic ewes by reverse-transcriptase PCR, as well as the mRNAs encoding the BMP type I receptors, BMPR-IA (activin-receptor-like kinase (ALK)-3) and BMPR-IB (ALK-6), and type II receptors (BMPR-II). Immunolabeling of pituitary sections revealed the presence of BMPR-IA (ALK-3) and BMPR-II in gonadotrope cells. To investigate the potential effects of BMPs on FSH secretion, ewe pituitary cell cultures were treated with BMP-4 (10−11 M to 10−9 M) for 48 h. Interestingly, FSH release was decreased in a dose-dependent manner. At 10−9 M BMP-4 both FSH concentration and FSHβ mRNA expression were reduced by 40% of control values. In contrast, there was no inhibitory effect on either LH or LHβ mRNA expression. A similar result was found with BMP-6. BMP-4 triggered the phosphorylation of Smad1, suggesting that the effect of BMP-4 on FSH secretion is due to the activation of the BMPs signaling pathway. Furthermore, BMP-4 blocked the stimulatory effect of activin on both FSH release and FSHβ mRNA and amplified the suppression of FSH release and FSHβ mRNA levels induced by 17β-estradiol. These results indicate that a functional BMP system operates within the sheep pituitary, at least in vitro, to decrease FSH release and to modulate the effect of activin.

scholarly journals CRTC2 and Nedd4 ligase involvement in FSH and TGFβ1 upregulation of connexin43 gap junction

2015 ◽  
Vol 55 (3) ◽  
pp. 263-275 ◽  
Author(s):  
Wei-Ling Fang ◽  
Si-Yi Lai ◽  
Wei-An Lai ◽  
Ming-Ting Lee ◽  
Ching-Fong Liao ◽  
...  
Keyword(s):  
Gap Junction ◽  
Ubiquitin Ligase ◽  
Granulosa Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ovarian Follicle ◽  
Type I ◽  
Dependent Manner ◽  
Cx43 Expression ◽  
Ovarian Granulosa Cells

The major mission of the ovarian follicle is the timely production of the mature fertilizable oocyte, and this is achieved by gonadotropin-regulated, gap junction-mediated cell–cell communication between the oocyte and surrounding nurturing granulosa cells. We have demonstrated that FSH and transforming growth factor beta 1 (TGFβ1) stimulate Gja1 gene-encoded connexin43 (Cx43) gap junction formation/function in rat ovarian granulosa cells is important for their induction of steroidogenesis; additionally, cAMP-protein kinase A (PKA)- and calcium-calcineurin-sensitive cAMP response element-binding (CREB) coactivator CRTC2 plays a crucial role during steroidogenesis. This study was to explore the potential molecular mechanism whereby FSH and TGFβ1 regulate Cx43 synthesis and degradation, particularly the involvement of CRTC2 and ubiquitin ligase Nedd4. Primary culture of granulosa cells from ovarian antral follicles of gonadotropin-primed immature rats was used. At 48 h post-treatment, FSH plus TGFβ1 increased Cx43 level and gap junction function in a PKA- and calcineurin-dependent manner, and TGFβ1 acting through its type I receptor modulated FSH action. Chromatin-immunoprecipitation analysis reveals FSH induced an early-phase (45 min) and FSH+TGFβ1 further elicited a late-phase (24 h) increase in CRTC2, CREB and CBP binding to the Gja1 promoter. Additionally, FSH+TGFβ1 increased the half-life of hyper-phosphorylated Cx43 (Cx43-P2). Also, the proteasome inhibitor MG132 prevented the brefeldin A (blocker of protein transport through Golgi)-reduced Cx43-P2 level and membrane Cx43 gap junction plaque. This is associated with FSH+TGFβ1-attenuated Cx43 interaction with Nedd4 and Cx43 ubiquitination. In all, this study uncovers that FSH and TGFβ1 upregulation of Cx43 gap junctions in ovarian granulosa cells critically involves enhancing CRTC2/CREB/CBP-mediated Cx43 expression and attenuating ubiquitin ligase Nedd4-mediated proteosomal degradation of Cx43 protein.

Stretching-Induced Collagen Type I Synthesis in Human Tendon Fibroblasts Is Mediated by TGF-β1

2003 ◽  
Author(s):  
Guoguang Yang ◽  
Richard C. Crawford ◽  
James H.-C. Wang
Keyword(s):  
Protein Synthesis ◽  
Transforming Growth Factor Beta ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Collagen Type I ◽  
Type I ◽  
Dependent Manner ◽  
Gene And Protein Expression ◽  
Mechanical Stretching ◽  
Tgf Β1

This study investigated the effect of cyclic mechanical stretching on the collagen gene expression and protein synthesis of human patellar tendon fibroblasts (HPTFs). We hypothesized that cyclic mechanical stretching of HPTFs would increase collagen synthesis via transforming growth factor-beta 1 (TGF-β1). To test the hypothesis, the tendon fibroblasts were cultured on microgrooved surfaces of silicone dishes under serum-free conditions. The cells were subjected to cyclic uniaxial stretching with a constant frequency and duration (0.5Hz, 4hr), and one of three stretching magnitudes (no stretch, 4%, and 8%) followed by 4 hours of rest. It was found that the gene and protein expression of both collagen type I and TGF-β1 were significantly increased in a stretching-magnitude dependent manner, whereas collagen type III gene and protein levels were not significantly changed. The exogenous addition of antibody to TGF-β1 eliminated the stretching-induced increase in collagen type I protein synthesis. The results therefore confirmed our working hypothesis and suggest that mechanical stretching of tendon fibroblasts can lead to matrix remodeling by modulating the collagen production of tendon fibroblasts, a process at least particially mediated by TGF-β1.

scholarly journals TRANSFORMING GROWTH FACTOR BETA OF TESTIS GERMINAL CELL IN GUINEA PIG (CAVIA PORCELLUS) AFTER EXPOSURE TO METHANOL EXTRACT OF THE SEEDS OF BITTER MELON (MOMORDICA CHARANTIA) AND DEPOT MEDROXYPROGESTERONE ACETATE

2018 ◽  
Vol 11 (12) ◽  
pp. 149 ◽  
Author(s):  
Syafruddin Ilyas ◽  
Salomo Hutahaean ◽  
Nursal Nursal
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Medroxyprogesterone Acetate ◽  
Transforming Growth Factor ◽  
Methanol Extract ◽  
Seed Extract ◽  
Control Group ◽  
Bitter Melon ◽  
Melon Seed ◽  
Depot Medroxyprogesterone Acetate

Objective: The discovery of male contraceptive drugs continues to be pursued, due to the very small participation of men associated with the lack of contraceptiveÐptions for men. The combination of methanol extract of bitter melon seed and depot medroxyprogesterone acetate (DMPA) becomes the choice that currently being pursued to be applied to men.Methods: The use of guinea pigs as experimental animals conducted research using experimental methods with complete randomized design. The study was divided into four control groups i.e K0; dimethylsulfoxide (DMSO) for 0 week (4 h),K1; Control group of DMSO for 4 weeks, K2; Control group of DMSO for 8 weeks, K3; Control group of DMSO for 12 weeks, and four treatment groups, i.e: group P0; bitter melon seed extract of 50 mg/100g body weight/day for 0 week (4 h), group P1; Bitter melon seed extract of 50 mg/100g BW/day for 4 weeks+DMPA, group P2; Bitter melon seed extract of 50 mg/100g BW/day for 8 weeks+DMPA, P3 group; Bitter melon seed extract of 50 mg/100g BW/day for 12 weeks+DMPA.Results: There was a significant effect (p<0.05) methanol extract of bitter melon seed to increase the transforming growth factor expression -β expression.Conclusion: The methanol extract of bitter melon seed was able to be candidate for herbal contraception.

scholarly journals Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2421
Author(s):  
Saray Tabak ◽  
Sofia Schreiber-Avissar ◽  
Elie Beit-Yannai
Keyword(s):  
Oxidative Stress ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Additional Treatment ◽  
Type I ◽  
Open Angle ◽  
Outflow Resistance ◽  
Stress Injury

Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.

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