Abstract:
:The epithelial-mesenchymal transition (EMT) is a critical stage during the development of silicosis fibrosis. In the current study, we hypothesized that the anti-fibrotic tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) may exert its anti-fibrotic effects via activation of the TGF-β1/ROCK1 pathway, leading to inhibition of EMT. To address this hypothesis, we first examined the effect of Ac-SDKP upon EMT using an in vivo rat silicosis model, as well as in an in vitro model of TGF-β1-induced EMT. Confocal laser scanning microscopy was used to examine colocalization of surfactant protein A (SP-A), fibroblast specific protein-1 (FSP-1) and α-smooth muscle actin (α-SMA) in vivo. Western blot analysis was used to examine for changes in the protein levels of E-cadherin (E-cad) and SP-A (epithelial cell markers), vimentin (mesenchymal cell marker), α-SMA (active myofibroblast marker), and collagen I and III in both in vivo and in vitro experiments. Secondly, we utilized Western blot analysis and confocal laser scanning microscopy to examine the protein expression of TGF-β1 and ROCK1 in in vivo and in vitro studies. The results revealed that Ac-SDKP treatment prevented increases in the expression of mesenchymal markers as well as TGF-β1, ROCK1, collagen I and III. Furthermore, Ac-SDKP treatment prevented decreases in the expression of epithelial cell markers in both in vivo and in vitro experiments. Based on the results, we conclude that Ac-SDKP inhibits the transition of epithelial cell-myofibroblast in silicosis via activation of the TGF-β1/ROCK1 signaling pathway, which may serve as a novel mechanism by which it exerts its anti-fibrosis properties.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Deng H,Xu H,Zhang X,Sun Y,Wang R,Brann D,Yang Fdoi
10.1016/j.taap.2016.01.010subject
Has Abstractpub_date
2016-03-01 00:00:00pages
1-10eissn
0041-008Xissn
1096-0333pii
S0041-008X(16)30011-4journal_volume
294pub_type
杂志文章abstract::A case study was conducted, using dibutyl phthalate (DBP), to explore an approach to using toxicogenomic data in risk assessment. The toxicity and toxicogenomic data sets relative to DBP-related male reproductive developmental outcomes were considered conjointly to derive information about mode and mechanism of action...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.09.006
更新日期:2013-09-15 00:00:00
abstract::The Bcl-2 family contains a panel of proteins which are conserved regulators of apoptosis in mammalian cells, like the anti-apoptotic protein Bcl-2. According to its significant role in altering susceptibility to apoptosis, the deciphering of the mechanism of Bcl-2 expression modulation may be crucial for identifying ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.07.010
更新日期:2011-10-01 00:00:00
abstract::Sulfur mustard (SM) is a chemical warfare agent that targets skin where it induces large blisters. DNA alkylation is a critical step to explain SM-induced cutaneous symptoms. We determined the kinetics of formation of main SM-DNA adducts and compare it with the development of the SM-induced pathogenesis in skin. SKH-1...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.10.010
更新日期:2013-12-15 00:00:00
abstract::Calcium uptake in cells occurs through specific membrane channels. Since cadmium and mercury inhibit calcium uptake, this study examined whether the calcium channels may also be involved in the uptake of these metals. Primary cultures of rat hepatocytes were incubated with 3 microM CdCl2 or HgCl2 in the absence or pre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(05)80018-3
更新日期:1991-09-01 00:00:00
abstract::Organic UV filters including benzophenone-3 (BP-3) are widely used to protect humans and materials from damage by UV irradiation. Despite the environmental occurrence of BP-3 in the aquatic environment, little is known about its effects and modes of action. In the present study we assess molecular and physiological ef...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.06.008
更新日期:2012-09-01 00:00:00
abstract::Cadmium (Cd(2+)) is a widespread environmental pollutant, which is associated with a wide variety of cytotoxic and metabolic effects. Recent studies showed that intoxication with the heavy metal most importantly targets the integrity of the epithelial barrier. In our study, the lung epithelial cell line, NCI H441, was...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.04.002
更新日期:2010-06-15 00:00:00
abstract::Carbon tetrachloride (CCl4) has been studied extensively for its hepatotoxic effects. There is a paucity of information, however, about its tissue deposition following administration by different routes and patterns of exposure. The specific objective of this study was to delineate the uptake, distribution, and elimin...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.8079
更新日期:1997-03-01 00:00:00
abstract::The present study examined the activation of protein kinase C (PKC) and disruption of Ca2+ homeostasis as potential mechanisms underlying effects of the polychlorinated biphenyl (PCB) congener 2,2'-dichlorobiphenyl (DCB) on inositol phosphate (IP) signaling in cerebellar granule cells. DCB (100 microM) increased basal...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0311
更新日期:1996-12-01 00:00:00
abstract::The InnoMed PredTox consortium was formed to evaluate whether conventional preclinical safety assessment can be significantly enhanced by incorporation of molecular profiling ("omics") technologies. In short-term toxicological studies in rats, transcriptomics, proteomics and metabolomics data were collected and analyz...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.09.022
更新日期:2011-04-15 00:00:00
abstract:UNLABELLED:Acetaminophen (APAP) overdose causes severe hepatotoxicity in animals and humans. However, the mechanisms underlying the gender differences in susceptibility to APAP overdose in mice have not been clarified. In our study, APAP (300mg/kg) caused severe liver injury in male mice but 69-77% lower injury in fema...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.09.002
更新日期:2014-11-15 00:00:00
abstract::Tolerance to several toxic effects of Cd, including lethality, has been shown following pretreatment with Cd. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity. Rats were challenged with Cd (2.0, 3.0, 4.0, or 5.0 mg/kg, iv) 24 hr after pretreatment with saline (2 ml/kg, sc) o...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90283-7
更新日期:1984-07-01 00:00:00
abstract::Metoclopramide (MCA) and procainamide (PCA), two widely used benzamide drugs developed before the present regulatory climate but recently found to induce DNA breaks in human lymphocytes, were evaluated for their genotoxic effects in cultured rodent and human cells. In subtoxic concentrations neither MCA (from 0.10 to ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1060
更新日期:1995-04-01 00:00:00
abstract::Acetaminophen (N-Acetyl-p-Aminophenol or APAP)-induced hepatotoxicity is the most common cause of acute liver failure in the United States and Western Europe. Previous studies have shown that TGFβ1 is elevated during APAP-induced hepatotoxicity and promotes liver injury by reducing liver regeneration while inducing he...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.115323
更新日期:2020-12-15 00:00:00
abstract::The effect of tamoxifen on Ca(2+) signaling and viability in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Tamoxifen evoked a rise in cytosolic free Ca(2+) levels ([Ca(2+)](i)) concentration-dependently between 1 and 50 microM with an EC50 of 10 microM. The response was dec...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2000.9011
更新日期:2000-10-01 00:00:00
abstract::Based on the observation that congenic haired and hairless mice differ in the hyperkeratinizing/hyperproliferative epidermal response following topical exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vivo, it has been proposed that this response in mice segregates with the Ah locus (which controls for the Ah...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90173-6
更新日期:1987-06-15 00:00:00
abstract::4-Alkylbicyclophosphates, R1C(CH2O)3P(O), with suitable R1 substituents (e.g., t-butyl, isopropyl, or cyclohexyl) are highly toxic compounds [mouse intraperitoneal (ip) LD50 values 0.036-0.52 mg/kg] and are potent noncompetitive gamma-aminobutyric acid (GABA) antagonists. 4-Alkylmonocyclophosphates of the type R1(HOCH...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90119-x
更新日期:1985-10-01 00:00:00
abstract::The pharmacokinetics of the industrially important compound triethylamine (TEA) and its metabolite triethylamine-N-oxide (TEAO) were studied in four volunteers after oral and intravenous administration. TEA was efficiently absorbed from the gastrointestinal (GI) tract, rapidly distributed, and in part metabolized into...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90300-1
更新日期:1989-09-15 00:00:00
abstract::Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione - AC-4; (5ZE)-5-acridin-9-y...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.01.010
更新日期:2013-04-01 00:00:00
abstract::An earlier study indicated that percutaneous absorption of a 40-nmol dose of TCDD decreased with aging in rats, suggesting that the potential for systemic exposure following dermal contact would be decreased in older age groups. In this study, maturational changes in potential for systemic exposure to TCDD following d...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1062
更新日期:1993-04-01 00:00:00
abstract::To assess aluminum toxicity to the A1-exposed lactating organism and her suckling offspring, lactating rabbits received 20, sc, A1 lactate injections (0, 25, 100, 400, or 800 mumol A1/kg/inj) between Days 4 and 29 postpartum. Offspring were weaned Day 30 postpartum. Weight gain in the first 12 postnatal weeks was slig...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90073-5
更新日期:1984-08-01 00:00:00
abstract::The biochemical mechanism involved in cadmium-induced cellular injury remains to be elucidated. Various theories have been proposed to account for this action, one of which is an interaction with reduced sulfhydryl (SH) groups of membranes. The ability of a known SH group reducing agent, dithiothreitol (DTT), to inter...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(86)90197-3
更新日期:1986-02-01 00:00:00
abstract::Benzo[a]pyrene (BaP), a polyaromatic hydrocarbon produced by the combustion of cigarettes and coke ovens, is a known procarcinogen. BaP activates the aryl hydrocarbon receptor (AhR) and induces the expression of a battery of genes, including CYP1A1, which metabolize BaP to toxic compounds. The possible role of CYP1 en...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.02.009
更新日期:2008-07-15 00:00:00
abstract::The kidneys are the primary organ for the accumulation and toxicity of inorganic mercury. In these studies the molecular response of precision-cut rabbit renal cortical slices to low levels of inorganic mercury was examined. Cortical slices (275 microm) were obtained from 1.0 kg NZW rabbits and exposed to mercuric chl...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1999.8772
更新日期:1999-11-01 00:00:00
abstract::The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2017.07.019
更新日期:2017-10-01 00:00:00
abstract::Human bladder cancer has been associated with chronic exposure to arsenic. Chronic exposure of an immortalized non-tumorigenic urothelial cell line (UROtsa cells) to arsenicals has transformed these cells to a malignant phenotype, but the involved mechanisms are not fully understood. Chronic inflammation has been link...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.12.029
更新日期:2010-04-15 00:00:00
abstract::The Fluorescent Cell Chip for in vitro immunotoxicity testing employs cell lines derived from lymphocytes, mast cells, and monocytes-macrophages transfected with various EGFP cytokine reporter gene constructs. While cytokine expression is a valid endpoint for in vitro immunotoxicity screening, additional marker for th...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2005.01.052
更新日期:2005-09-01 00:00:00
abstract::The effect of age and sex on the elimination of theophylline in New Zealand White rabbits was investigated following exposure to 0.3 ppm of ozone (O3) for 3.75 hr/day over 5 consecutive days. Animals were given air alone 5 to 7 days before and after the 5 days of O3 exposure. The elimination half-life of theophylline ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90118-8
更新日期:1985-10-01 00:00:00
abstract::Nutrient availability is one of the major non-genetic factors determining embryonic growth and larval or fetal size. Due to the high human consumption of blood lipid regulators, fibrates have recently been reported as pollutants in rivers. Our study investigated the developmental toxicity of fibrates in zebrafish. Tre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.11.016
更新日期:2008-05-01 00:00:00
abstract::Previous experiments showed that treatment of mice and rats with thioacetamide (TAA) induced liver cell damage, fibrosis and/or cirrhosis, associated with increased oxidative stress and activation of hepatic stellate cells. Some experiments suggest that CYP2E1 may be involved in the metabolic activation of TAA. Howeve...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.11.010
更新日期:2008-05-01 00:00:00
abstract::Though nanomaterials (NMs) are being utilized worldwide, increasing use of NMs have raised concerns over their safety to human health and environment. Iron oxide (Fe(2)O(3)) NMs have important applications. The aim of this study was to assess the genotoxicity of Fe(2)O(3)-30nm and Fe(2)O(3)-bulk in female Wistar rats....
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.10.016
更新日期:2013-01-01 00:00:00