共查询到20条相似文献,搜索用时 15 毫秒
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P. Locci Tiziano Baroni Furio Pezzetti Cinzia Lilli Lorella Marinucci Domenica Martinese Ennio Becchetti Mario Calvitti Francesco Carinci 《Cell and tissue research》1999,297(3):475-483
The phenotype of Apert osteoblasts differs from that of normal osteoblasts in the accumulation of macromolecules in the extracellular matrix. Apert osteoblasts increase type I collagen, fibronectin and glycosaminoglycans secretion compared with normal osteoblasts. Because the extracellular matrix macromolecule accumulation is greatly modulated by transforming growth factor-beta(1), we examined the ability of normal and Apert osteoblasts to secrete transforming growth factor-beta(1) by CCL-64 assay and to produce transforming growth factor-beta(1 )by analysis of the mRNA expression of transforming growth factor-beta(1). Northern blot analysis revealed an increased amount of transforming growth factor-beta(1) mRNA expression in Apert osteoblasts compared with normal ones. Moreover, the level of the active transforming growth factor-beta(1) isoform was higher in Apert than in normal media. In pathologic cells, the increase in transforming growth factor-beta(1) gene expression was associated with a parallel increase in the factor secreted into the medium. The level of transforming growth factor-beta(1) was decreased by the addition of basic fibroblast growth factor. Transforming growth factor-beta(1) is controlled temporally and spatially during skeletal tissue development and produces complex stimulatory and inhibitory changes in osteoblast functions. We hypothesise that in vitro differences between normal and Apert osteoblasts may be correlated to different transforming growth factor-beta(1) cascade patterns, probably due to an altered balance between transforming growth factor-beta(1) and basic fibroblast growth factor. 相似文献
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《Theriogenology》1996,45(8):1463-1472
The mammalian ovarian cycle is a strictly regulated process that is dependent on the intimate interactions among the 3 cell types in the follicle — theca, granulosa, and oocyte. The cycle has been shown to be controlled by gonadotropins as well as locally produced peptide factors. In this study, an in vitro culture system was used to study the roles of 2 locally produced ovarian peptide factors, transforming growth factor-β1 (TGF-β1) and activin-A, on porcine granulosa cell steroidogenesis. Gonadotropin stimulated cultured porcine granulosa cells (from medium-sized follicles) were pretreated with 100 ng/ml follicle-stimulating hormone (FSH) for 48 h and then treated with 1 ng/ml TGF-β1, 100 ng/ml activin-A, TGF-β1 plus activin-A, or received no treatment (control) for 48 h, From our previous studies, the concentrations of the 2 growth factors were determined to produce maximal antisteroidogenic effects in porcine granulosa cells. Progesterone (P4) production, estradiol-17β (E2) production, and aromatase activity for gonadotropin-stimulated porcine granulosa cells treated with TGF-β1, activin-A, and TGF-β1 plus activin-A were significantly (P < 0.05) reduced fromthat of the control. The same procedures were conducted on basal steroidogenesis studies in which no pretreatment with FSH was performed. Both P4 and E2 production and aromatase activity for porcine granulosa cells treated with TGF-β1, activin-A and TGF-β1 plus activin-A were significantly (P < 0.05) inhibited compared with the control. Our results indicate that both TGF-β1 and activin-A can inhibit FSH-stimulated and basal steroidogeneses in porcine granulosa cells and, thus, may act as local atretic factors during follicular development. When the 2 growth factors were given in combination at concentrations that would produce maximal steroidogenic inhibition, they were not able to produce a synergistic effect. These results are consistent with the current theory that TGF-β1 and activin-A may act via the same messenger system, a serine-threonine kinase. 相似文献
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Li Ke Zhou Rong Ma Mingze Jin Chaomei Jiao Linlin Zhang Siyu Tian Mei Zhou Fang 《Molecular biology reports》2022,49(10):9325-9333
Molecular Biology Reports - Epithelial-to-mesenchymal transition (EMT) is the process by which epithelial cells transform into mesenchymal cells, which plays a significant role in lung fibrotic... 相似文献
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Cory J. Xian 《Histochemistry and cell biology》1999,111(6):467-475
The expression and function of transforming growth factor alpha (TGF-α) in the kidney are not fully characterised. There exists
controversy concerning the detection of renal TGF-α mRNA and the localisation of its immunoreactivity. In attempts to clarify
the detection and localisation issue, the present study aimed to detect TGF-α mRNA in neonate and adult rat kidneys, to examine
the specificity of two commonly used anti-TGF-α antibodies and finally to localise renal TGF-α immunoreactivity using a specific
antibody. TGF-α mRNA of around 4.8 kb was readily detected with a sensitive non-radioactive northern analysis, with a similar
abundance in neonatal and adult rat kidneys. Renal TGF-α peptide of the 6-kDa mature form was identified by western blotting.
By using various controls, including specimens from TGF-α knock out mice in comparison with wild-type mice, the present study
has confirmed the specificity of a polyclonal anti-human recombinant TGF-α antibody. With this antibody, TGF-α immunoreactivity
was localised to the proximal tubules in renal cortex. In addition, the present study has also demonstrated a non-specificity
in localising TGF-α in rodent kidneys by the most commonly used monoclonal anti-human TGF-α C-terminal peptide antibody, which
stained collecting ducts in renal cortex and medulla.
Accepted: 8 April 1999 相似文献
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M Bonora E De Marchi S Patergnani J M Suski F Celsi A Bononi C Giorgi S Marchi A Rimessi J Duszyński T Pozzan M R Wieckowski P Pinton 《Cell death and differentiation》2014,21(8):1198-1208
Mitochondrial defects, affecting parameters such as mitochondrial number and shape, levels of respiratory chain complex components and markers of oxidative stress, have been associated with the appearance and progression of multiple sclerosis. Nevertheless, mitochondrial physiology has never been monitored during oligodendrocyte progenitor cell (OPC) differentiation, especially in OPCs challenged with proinflammatory cytokines. Here, we show that tumor necrosis factor alpha (TNF-α) inhibits OPC differentiation, accompanied by altered mitochondrial calcium uptake, mitochondrial membrane potential, and respiratory complex I activity as well as increased reactive oxygen species production. Treatment with a mitochondrial uncoupler (FCCP) to mimic mitochondrial impairment also causes cells to accumulate at the progenitor stage. Interestingly, AMP-activated protein kinase (AMPK) levels increase during TNF-α exposure and inhibit OPC differentiation. Overall, our data indicate that TNF-α induces metabolic changes, driven by mitochondrial impairment and AMPK activation, leading to the inhibition of OPC differentiation.Multiple sclerosis (MS) is a neurological disorder of the central nervous system that is characterized by demyelination and neurodegeneration. Although the pathogenesis of MS is not completely understood, various findings suggest that immune-mediated loss of myelin and different types of mitochondrial dysfunction are associated with this disease.1 Mitochondria are often described as cellular powerhouses that utilize oxygen to produce adenosine triphosphate (ATP), a molecule that is critical for most cellular functions.2 In addition, mitochondria are the major sites of the intracellular production of highly reactive free radicals that, if not neutralized, alter cellular metabolism and damage cellular components.3In several studies, mitochondrial dysfunction has been reported to be frequently associated with demyelination, whereas proper function is required for correct oligodendrocyte differentiation and myelination.4, 5 Furthermore, there is in vitro evidence that cytokine-induced oligodendrocyte injury involves mitochondrial dysfunction.6 One cytokine that is of particular interest in MS is tumor necrosis factor alpha (TNF-α). Evidence implicating TNF-α in the underlying pathology of MS includes: (i) reports that MS patients have elevated TNF-α levels at the sites of active MS lesions at autopsy,7 (ii) reports that TNF-α levels are elevated in the cerebrospinal fluid and serum of individuals with MS compared with unaffected individuals and that these TNF-α levels correlate with the severity of the lesions.8, 9Moreover, it has been widely reported that TNF-α is able to impair oligodendrocyte differentiation and that in leukemia cell lines, TNF-α-induced cell death requires impairments in the activity of mitochondrial respiratory chain complex I. Complex I is strategically important for regulating ATP synthesis and is one of the most important sources of reactive oxygen species (ROS) within cells.10 Despite this evidence, the relationships between mitochondrial physiology, TNF-α, and oligodendrocyte differentiation have not yet been examined. This study addressed the hypothesis that the impairment of oligodendrocyte differentiation caused by TNF-α exposure is causally linked to altered mitochondrial physiology. 相似文献
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Fayong Luo Yan Zhuang Mark D Sides Cecilia G Sanchez Bin Shan Eric S White Joseph A Lasky 《Respiratory research》2014,15(1):51
Background
Idiopathic pulmonary fibrosis (IPF) is a progressive disease of insidious onset, and is responsible for up to 30,000 deaths per year in the U.S. Excessive production of extracellular matrix by myofibroblasts has been shown to be an important pathological feature in IPF. TGF-β1 is expressed in fibrotic lung and promotes fibroblast to myofibroblast differentiation (FMD) as well as matrix deposition.Methods
To identify the mechanism of Arsenic trioxide’s (ATO)’s anti-fibrotic effect in vitro, normal human lung fibroblasts (NHLFs) were treated with ATO for 24 hours and were then exposed to TGF-β1 (1 ng/ml) before harvesting at multiple time points. To investigate whether ATO is able to alleviate lung fibrosis in vivo, C57BL/6 mice were administered bleomycin by oropharyngeal aspiration and ATO was injected intraperitoneally daily for 14 days. Quantitative real-time PCR, western blotting, and immunofluorescent staining were used to assess the expression of fibrotic markers such as α-smooth muscle actin (α-SMA) and α-1 type I collagen.Results
Treatment of NHLFs with ATO at very low concentrations (10-20nM) inhibits TGF-β1-induced α-smooth muscle actin (α-SMA) and α-1 type I collagen mRNA and protein expression. ATO also diminishes the TGF-β1-mediated contractile response in NHLFs. ATO’s down-regulation of profibrotic molecules is associated with inhibition of Akt, as well as Smad2/Smad3 phosphorylation. TGF-β1-induced H2O2 and NOX-4 mRNA expression are also blocked by ATO. ATO-mediated reduction in Smad3 phosphorylation correlated with a reduction of promyelocytic leukemia (PML) nuclear bodies and PML protein expression. PML-/- mouse embryonic fibroblasts (MEFs) showed decreased fibronectin and PAI-1 expression in response to TGF-β1. Daily intraperitoneal injection of ATO (1 mg/kg) in C57BL/6 mice inhibits bleomycin induced lung α-1 type I collagen mRNA and protein expression.Conclusions
In summary, these data indicate that low concentrations of ATO inhibit TGF-β1-induced fibroblast to myofibroblast differentiation and decreases bleomycin induced pulmonary fibrosis. 相似文献13.
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《遗传学报》2022,49(4):269-278
Nonalcoholic steatohepatitis (NASH), an inflammatory subtype of nonalcoholic fatty liver disease, is featured by significantly elevated levels of various proinflammatory cytokines. Among numerous proinflammatory factors that contribute to NASH pathogenesis, the secreted protein, tumor necrosis factor-alpha (TNF-α), plays an essential role in multiple facets of NASH progression and is therefore considered as a potential therapeutic target. In this review, we will first systematically describe the preclinical studies on the biochemical function of TNF-α and its intracellular downstream signaling mechanisms through its receptors. Moreover, we extensively discuss its functions in regulating inflammation, cell death, and fibrosis of liver cells in the pathogenesis of NASH, and the molecular mechanism that TNF-α expression is regulated by NF-κB and other upstream master regulators during NASH progression. As TNF-α is one of the causal factors that remarkably contributes to NASH progression, combination of therapeutic modalities, including TNF-α-based therapies may lead to the resolution of NASH via multiple pathways and thus generate clinical benefits. For translational studies, we summarize recent advances in strategies targeting TNF-α and its signaling pathway, which paves the way for potential therapeutic treatments for NASH in the future. 相似文献
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Neural stem cells (NSCs) have been defined as neural cells with the potential to self-renew and eventually generate all cell types of the nervous system. NSCs serve as an ideal cell type for nervous system repair. In the present study, miR-146 overexpression and predicted target (notch 1) were used to study proliferation and differentiation of mouse NSCs. shRNA were used to demonstrate the function of Notch 1 in proliferation of mouse NSCs and luciferase reporter assay was used to assess and confirm the binding sequence of 3′-UTR between Notch 1 and miR-146. Results showed that miR-146 overexpression and knockdown of notch 1 inhibited proliferation of mouse NSCs under serum-free cultural conditions and promoted spontaneous differentiation of mouse NSCs under contained serum cultural conditions respectively. Mouse NSCs spontaneously underwent differentiation into neurogenic cells with contained serum medium. However, when miR-146 was overexpressed, differentiation efficiency of glial cells from NSCs was increased, suggesting that Notch1 promoted NSC proliferation and repressed spontaneous differentiation of NSC in serum-free medium. In conclusion, our results demonstrate that miR-146 promoted spontaneous differentiation of NSCs, and this mechanism was influenced by miR-146, as well as its target (notch 1) and downstream gene. 相似文献
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The epidermal growth factor (EGF) family of polypeptides is regulators for tissue development and repair, and is characterized
by the fact that their mature forms are proteolytically derived from their integral membrane precursors. This article reviews
roles of the prominent members of the EGF family (EGF, transforming growth factor-alpha [TGF-α] and heparin-binding EGF [HB-EGF])
and the related neuregulin family in the nerve system. These polypeptides, produced by neurons and glial cells, play an important
role in the development of the nervous system, stimulating proliferation, migration, and differentiation of neuronal, glial,
and Schwann precursor cells. These peptides are also neurotrophic, enhancing survival and inhibiting apoptosis of post-mitotic
neurons, probably acting directly through receptors on neurons, or indirectly via stimulating glial proliferation and glial
synthesis of other molecules such as neurotrophic factors. TGF-α, EGF, and neuregulins are involved in mediating glial-neuronal
and axonal-glial interactions, regulating nerve injury responses, and participating in injury-associated astrocytic gliosis,
brain tumors, and other disorders of the nerve system. Although the collective roles of the EGF family (as well as those of
the neuregulins) are shown to be essential for the nervous system, redundancy may exist among members of the EGF family. 相似文献
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Qin Y Zhong Y Dang L Zhu M Yu H Chen W Cui J Bian H Li Z 《Journal of Proteomics》2012,75(13):4114-4123
Although aberrant glycosylation of human glycoproteins is related to liver fibrosis that results from chronic damage to the liver in conjunction with the activation of hepatic stellate cells (HSCs), little is known about the precision alteration of protein glycosylation referred to the activation of HSCs by transforming growth factor-β1 (TGF-β1). The human HSCs, LX-2 were activated by TGF-β1. The lectin microarrays were used to probe the alteration of protein glycosylation in the activated HSCs compared with the quiescent HSCs. Lectin histochemistry was used to further validate the lectin binding profiles and assess the distribution of glycosidic residues in cells. As a result, 14 lectins (e. g. AAL, PHA-E, ECA and ConA) showed increased signal while 7 lectins (e. g. UEA-I and GNA) showed decreased signal in the activated LX-2 compared with the quiescent LX-2. Meanwhile, AAL, PHA-E and ECA staining showed moderate binding to the cytoplasma membrane in the quiescent LX-2, and the binding intensified in the same regions of the activated LX-2. In conclusion, the precision alteration of protein glycosylation related to the activation of the HSCs may provide useful information to find new molecular mechanism of HSC activation and antifibrotic therapeutic strategies. 相似文献
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