scholarly journals Syndecan-4 Deficiency Leads to High Mortality of Lipopolysaccharide-injected Mice

2001 ◽  
Vol 276 (50) ◽  
pp. 47483-47488 ◽  
Author(s):  
Kazuhiro Ishiguro ◽  
Kenji Kadomatsu ◽  
Tetsuhito Kojima ◽  
Hisako Muramatsu ◽  
Mitsunori Iwase ◽  
...  
Keyword(s):  
Growth Factor ◽  
High Mortality ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Endotoxin Shock ◽  
Left Ventricular ◽  
Wild Type ◽  
In The Wild ◽  
Deficient Mice ◽  
Fractional Shortening

Syndecan-4 is a transmembrane heparan sulfate proteoglycan belonging to the syndecan family. Following intraperitoneal injection of lipopolysaccharide (LPS), syndecan-4-deficient mice exhibited high mortality compared with wild-type controls. Severe endotoxin shock was observed in the deficient mice: systolic blood pressure and left ventricular fractional shortening were lower in the deficient mice than in the wild-type controls 9 h after LPS injection. Although histological examinations revealed no apparent differences between two groups, the plasma level of interleukin (IL)-1β was higher in the deficient mice than in the wild-type controls 9 h after LPS injection. Consistent with the regulatory roles of syndecan-4, its expression in monocytes and endothelial cells of microvasculature increased in the wild-type mice after LPS administration. Although IL-1β was produced to the same extent by macrophages from syndecan-4-deficient and wild-type mice after LPS stimulation, inhibition of its production by transforming growth factor-β1 was impaired in the syndecan-4-deficient macrophages. These results indicate that syndecan-4 could be involved in prevention of endotoxin shock, at least partly through the inhibitory action of transforming growth factor-β1 on IL-1β production.

scholarly journals Transforming growth factor β1 differently modulates wild‐type and TgF344‐AD astrocyte cultures' function

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Débora Guerini de Souza ◽  
Andreia Silva da Rocha ◽  
Giovanna Bortoluzzi Salles ◽  
Ana Cristina Laydner Joly Oliveira ◽  
Christian Limberger ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Wild Type

scholarly journals Osteoprotegerin expression in liver is induced by IL-13 through TGF-β

2020 ◽  
Author(s):  
Adhyatmika Adhyatmika ◽  
Kurnia SS Putri ◽  
Emilia Gore ◽  
Keri Mangnus ◽  
Catharina Reker-Smit ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Liver Tissue ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Experimental Models ◽  
Wild Type ◽  
3T3 Fibroblasts ◽  
Liver Slices ◽  
Deficient Mice

Backgrounds: Osteoprotegerin (OPG) is a profibrotic mediator produced by myofibroblasts under influence of transforming growth factor β (TGFβ). Its expression in experimental models of liver fibrosis correlates well with disease severity and treatment responses. The regulation of OPG in liver tissue is largely unknown and we therefore set out to elucidate which growth factors/interleukins associated with fibrosis induce OPG and through which pathways. Methods: Precision-cut liver slices of wild type and STAT6-deficient mice and 3T3 fibroblasts were used to investigate the effects of TGFβ, interleukin (IL) 13 (IL13), IL1β, and platelet-derived growth factor BB (PDGF-BB) on expression of OPG. Results: In addition to TGFβ, only IL13 and not PDGF-BB or IL1β could induce OPG expression in 3T3 fibroblasts and liver slices. This IL13-dependent induction was not shown in liver slices of STAT6-deficient mice and when wild type slices were cotreated with TGFβ receptor 1 kinase inhibitor galunisertib, STAT6 inhibitor AS1517499, or AP1 inhibitor T5224. This suggests that the OPG-inducing effect of IL13 is mediated through IL13 receptor α1-activation and subsequent STAT6-dependent upregulation of IL13 receptor α2, which in turn activates AP1 and induces production of TGFβ and subsequent production of OPG. Conclusion: We have shown that IL13 induces OPG release by liver tissue through a TGFβ-dependent pathway involving both the α1 and the α2 receptor of IL13 and transcription factors STAT6 and AP1. OPG may therefore be a novel target for the treatment liver fibrosis as it is mechanistically linked to two important regulators of fibrosis in liver, namely IL13 and TGFβ1.

scholarly journals Calcineurin deficiency decreases inflammatory lesions in transforming growth factor β1-deficient mice

2009 ◽  
Vol 158 (3) ◽  
pp. 317-324 ◽  
Author(s):  
R. Bommireddy ◽  
O. F. Bueno ◽  
J. Martin ◽  
I. Ormsby ◽  
H. Chen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Inflammatory Lesions ◽  
Deficient Mice

scholarly journals Transforming Growth Factor-β1—Modulated Cerebral Gene Expression

2002 ◽  
Vol 22 (9) ◽  
pp. 1114-1123 ◽  
Author(s):  
Sylvain Lesné ◽  
Sophie Blanchet ◽  
Fabian Docagne ◽  
Géraldine Liot ◽  
Laurent Plawinski ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cortical Neurons ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Wild Type ◽  
Chain Reactions ◽  
Polymerase Chain Reactions ◽  
Cultured Cortical Neurons ◽  
The Central Nervous System ◽  
Tgf Β1

Transforming growth factor-β1 (TGF-β1) plays a central role in the response of the brain to different types of injury. Increased TGF-β1 has been found in the central nervous system of patients with acute or chronic disorders such as stroke or Alzheimer disease. To further define the molecular targets of TGF-β1 in cerebral tissues, a selection of high-density cDNA arrays was used to characterize the mRNA expression profile of 7,000 genes in transgenic mice overexpressing TGF-β1 from astrocytes as compared with the wild-type line. Selected findings were further evaluated by reverse transcription-polymerase chain reactions from independent transgenic and wild-type mice. Furthermore, the expression pattern of seven selected genes such as Delta-1, CRADD, PRSC-1, PAI-1, Apo-1/Fas, CTS-B, and TβR-II were confirmed in either cultured cortical neurons or astrocytes following TGF-β1 treatment. The authors' observations enlarge the repertoire of known TGF-β1–modulated genes and their possible involvement in neurodegenerative processes.

scholarly journals Increased bleomycin-induced lung injury in mice deficient in the transcription factor T-bet

2006 ◽  
Vol 291 (4) ◽  
pp. L658-L667 ◽  
Author(s):  
Jianguo Xu ◽  
Ana L. Mora ◽  
John LaVoy ◽  
Kenneth L. Brigham ◽  
Mauricio Rojas
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
T Lymphocytes ◽  
Lung Injury ◽  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Wild Type ◽  
Th2 Polarization ◽  
Variable Sensitivity

The reasons for variable sensitivity among and within species to lung injury and fibrosis caused by bleomycin (BLM) are unknown. Because T helper (Th) 1 and 2 (Th1 and Th2) polarization of CD4+ T lymphocytes is one of the factors that affects the BLM response, we hypothesized that preventing expression of the Th1 transcription factor T-bet would render BLM-resistant BALB/c mice sensitive to BLM. Wild-type and T-bet-deficient (T-bet−/−) BALB/c mice were treated with BLM or saline solution intratracheally. After BLM treatment, collagen content in the lung increased twofold by day 14 in lungs from T-bet−/− mice but was unaffected in lungs from wild-type BALB/c mice. These findings were confirmed by collagen staining of histopathological sections. BLM treatment significantly increased respiratory frequency and decreased tidal volume by day 14 in T-bet−/− mice but had no effect in wild-type mice. Lung fibrosis in BLM-treated T-bet−/− mice was associated with increased circulating levels of Th2 cytokines and increased expression of the profibrotic factor transforming growth factor-β1. Depletion of CD4+, but not CD8+, T cells in T-bet−/− mice diminished BLM-induced lung fibrosis and the expression of transforming growth factor-β1. These data suggest that the T-bet pathway in CD4+ T lymphocytes can confer resistance to BLM-induced lung fibrosis in BALB/c mice.

scholarly journals Macrophage-Derived Legumain Promotes Pulmonary Hypertension by Activating the MMP (Matrix Metalloproteinase)-2/TGF (Transforming Growth Factor)-β1 Signaling

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Peiyuan Bai ◽  
Luheng Lyu ◽  
Tingting Yu ◽  
Caojian Zuo ◽  
Jie Fu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Right Ventricular ◽  
Transforming Growth Factor ◽  
Cysteine Proteinase ◽  
Active Form ◽  
Transforming Growth Factor Β1 ◽  
Left Ventricular ◽  
Matrix Metalloproteinase 2 ◽  
Ventricular Wall

Objective— Macrophages participate in the pathogenesis of pulmonary arterial hypertension (PAH). Lgmn (Legumain), a newly discovered cysteine proteinase belonging to the C13 peptidase family, is primarily expressed in macrophages; however, its roles in PAH remain unknown. Approach and Results— Herein, Lgmn was upregulated in lung tissues of PAH mice subjected to hypoxia plus SU5416 and PAH rats challenged with monocrotaline. Global Lgmn ablation and macrophage-specific ablation alleviated PAH compared with wild-type mice, evident from a reduction in right ventricular systolic pressure, the ratio of the right ventricular wall to the left ventricular wall plus the septum, the pulmonary vascular media thickness, and pulmonary vascular muscularization. Increased expression of ECM (extracellular matrix) proteins was correlated with MMP (matrix metalloproteinase)-2 activation and TGF (transforming growth factor)-β1 signaling in the PAs. Although Lgmn did not affect inflammatory cell infiltration and PA smooth muscle cell proliferation, it drove increased the synthesis of ECM proteins via MMP-2 activation. MMP-2 hydrolyzed the TGF-β1 precursor to the active form. An Lgmn-specific inhibitor markedly ameliorated PAH. Clinically, serum Lgmn levels were closely associated with the severity of idiopathic PAH. Conclusions— Our results indicate that Lgmn inhibition could be an effective strategy for preventing or delaying PAH.

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