Search results for "Transforming growth factor"
showing 10 items of 294 documents
Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool.
2015
Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression). In contrast to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration. Here we show by intravital microscopy in live mice that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermor…
Expression of a dominant negative type II TGF-β receptor in mouse skin results in an increase in carcinoma incidence and an acceleration of carcinoma…
1998
The role of Transforming growth factor beta (TGF-beta) in carcinogenesis is complex. There are reports on both tumor inhibition and tumor promotion by TGF-beta. To elucidate the complex role of TGF-beta in epithelial carcinogenesis, we generated transgenic mice overexpressing a dominant negative type II TGF-beta receptor in the basal cell compartment and in follicular cells of the skin. Despite the reduced responsiveness of transgenic keratinocytes to TGF-beta, both proliferation and differentiation were normal in non-irritated epidermis of these transgenic mice. Thus, interruption of signaling of all three isoforms of TGF-beta in basal and follicular cells does not disturb tissue homeostas…
Different integrins mediate cell spreading, haptotaxis and lateral migration of HaCaT keratinocytes on fibronectin
2000
Collaborative role of various fibronectin-binding integrins (alpha5beta1, alphavbeta1 and alphavbeta6) as mediators of cell adhesion and migration on fibronectin was studied using cultured HaCaT keratinocytes. This cell line spontaneously expressed all three fibronectin-binding integrins. In addition, the expression of alphavbeta6 integrin was strongly and specifically upregulated by transforming growth factor-beta1 (TGFbeta1) whereas the amount of other integrins remained practically unchanged on the cell surface. Adhesion, spreading and motility of HaCaT keratinocytes on fibronectin were promoted by TGFbeta1. Based on antibody blocking experiments, both untreated and TGFbeta1-treated HaCa…
The Influence of Adalimumab and Cyclosporine A on the Expression Profile of the Genes Related to TGFβ Signaling Pathways in Keratinocyte Cells Treate…
2020
Background. In the treatment of moderate to severe psoriasis, cyclosporine A (CsA) conventional therapy is used and biological, anti-cytokine treatment using, for example, anti-TNF drug—adalimumab. Aim. This study aimed at investigating the effect of CsA and adalimumab on the profile of mRNAs and protein expression associated with transforming growth factor β (TGFβ) pathways in human keratinocyte (HaCaT) culture previously exposed to lipopolysaccharide (LPS). Materials and Methods. HaCaT culture was exposed to 1 ng/ml LPS for 8 hours+8 μg/ml adalimumab for 2, 8, and 24 hours or 1 ng/ml LPS for 8 hours+100 ng/ml CsA for 2, 8, and 24 hours and compared to the control culture. Sulphorodamine B…
Resistance of keratinocytes to TGFbeta-mediated growth restriction and apoptosis induction accelerates re-epithelialization in skin wounds.
2002
The pleiotropic growth factor TGFβ plays an important role in regulating responses to skin injury. TGFβ targets many different cell types and is involved in all aspects of wound healing entailing inflammation,re-epithelialization, matrix formation and remodeling. To elucidate the role of TGFβ signal transduction in keratinocytes during cutaneous wound healing, we have used transgenic mice expressing a dominant negative type II TGFβ receptor exclusively in keratinocytes. We could demonstrate that this loss of TGFβ signaling in keratinocytes led to an accelerated re-epithelialization of full thickness excisional wounds accompanied by an increased proliferation in keratinocytes at the wound ed…
Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor pathway in nasal cells
2014
Leptin is involved in the lung epithelial homeostasis. Its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure leading to consequential structural abnormalities in the nasal epithelium. Topical corticosteroids are recommended as first-line therapy in AR. Parietaria pollen is one of the most important allergenic sources in the southern Europe. In vitro, in human nasal epithelial cell line RPMI 2650, we aimed to determine whether allergen stimulation acts on leptin/leptin receptor pathway and how fluticasone furoate (FF) influences this pathway. The effects of the major allergen recombinant Par j 1 (rPar j 1), of FF, of leptin, and of TGF-b1 …
HSP27 controls GATA-1 protein level during erythroid cell differentiation.
2010
AbstractHeat shock protein 27 (HSP27) is a chaperone whose cellular expression increases in response to various stresses and protects the cell either by inhibiting apoptotic cell death or by promoting the ubiquitination and proteasomal degradation of specific proteins. Here, we show that globin transcription factor 1 (GATA-1) is a client protein of HSP27. In 2 models of erythroid differentiation; that is, in the human erythroleukemia cell line, K562 induced to differentiate into erythroid cells on hemin exposure and CD34+ human cells ex vivo driven to erythroid differentiation in liquid culture, depletion of HSP27 provokes an accumulation of GATA-1 and impairs terminal maturation. More spec…
NFATc1 Induction in Peripheral T and B Lymphocytes
2013
Abstract NFAT transcription factors control the proliferation and survival of peripheral lymphocytes. We have reported previously that the short isoform NFATc1/αA whose generation is induced by immune receptor stimulation supports the proliferation and inhibits the activation-induced cell death of peripheral T and B cells. We will show in this study that in novel bacterial artificial chromosome transgenic mice that express EGFP under the control of entire Nfatc1 locus the Nfatc1/Egfp transgene is expressed as early as in double-negative thymocytes and in nonstimulated peripheral T and B cells. Upon immune receptor stimulation, Nfatc1/Egfp expression is elevated in B, Th1, and Th2 cells, but…
Hepatic over-expression of TGF-beta1 promotes LPS-induced inflammatory cytokine secretion by liver cells and endotoxemic shock.
2005
Transforming growth factor-beta (TGF-beta) is an important suppressor of inflammation. However, TGF-beta has also been found to promote secretion of inflammatory cytokines, and transgenic mice, which constitutively express TGF-beta in liver, have been found to be more susceptible to endotoxemia. To approach this apparent paradox, we investigated the role of hepatic TGF-beta1 in endotoxemia by utilising inducible TGF-beta1-transgenic mice that express TGF-beta1 under control of the C-reactive protein promoter. In contrast to non-transgenic littermates, administration of lipopolysaccharide (LPS) induced strongly increased expression of TGF-beta and acute phase proteins in the TGF-beta1-transg…
Liver fibrosis: Direct antifibrotic agents and targeted therapies
2018
Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C. Highly effective antiviral therapy can prevent progression or even induce reversal in the majority of patients, but such treatment remains elusive for the majority of liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic or autoimmune liver diseases. Moreover, drugs that would speed…