scholarly journals Plasma Levels of a Cleaved Form of Galectin-9 Are the Most Sensitive Biomarkers of Acquired Immune Deficiency Syndrome and Tuberculosis Coinfection

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1495
Author(s):  
Shirley T. Padilla ◽  
Toshiro Niki ◽  
Daisuke Furushima ◽  
Gaowa Bai ◽  
Haorile Chagan-Yasutan ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Transforming Growth Factor ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Matricellular Proteins ◽  
Characteristic Analysis ◽  
Pulmonary Tb ◽  
Transforming Growth Factor Α ◽  
Mdr Tb ◽  
Factor Α

Acquired immunodeficiency syndrome (AIDS) complicated with tuberculosis (TB) is a global public issue. Due to the paucity of bacteria in AIDS/TB, blood-based biomarkers that reflect disease severity are desired. Plasma levels of matricellular proteins, such as osteopontin (OPN) and galectin-9 (Gal-9), are known to be elevated in AIDS and TB. Therefore, full-length (FL)-Gal9 and FL-OPN, and their truncated forms (Tr-Gal9, Ud-OPN), and 38 cytokines/chemokines were measured in the plasma of 24 AIDS (other than TB), 49 TB, and 33 AIDS/TB patients. Receiver-operating characteristic analysis was used to screen molecules that could distinguish either between disease and normal group, among each disease group, or between deceased patients and survivors. Selected molecules were further analyzed for significant differences. Tr-Gal9 had the highest ability to differentiate TB from AIDS or AIDS/TB, while Ud-OPN distinguished multidrug resistance (MDR)-TB from non-MDR TB, and extra-pulmonary TB from pulmonary TB. Molecules significantly elevated in deceased patients included; FL-Gal9, Tr-Gal9, interleukin (IL)-1 receptor antagonist, IL-17A and transforming growth factor-α in AIDS; IL-6, granulocyte colony-stimulating factor and monocyte chemotactic protein-1 in TB; and macrophage inflammatory protein-1β in AIDS/TB. From the sensitivity, specificity, and significant elevation, Tr-Gal9 is the best biomarker of inflammation and severity in AIDS and AIDS/TB.

scholarly journals Transforming growth factor-α in the mammalian brain

1989 ◽  
Vol 264 (7) ◽  
pp. 3880-3883
Author(s):  
J E Kudlow ◽  
A W Leung ◽  
M S Kobrin ◽  
A J Paterson ◽  
S L Asa
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mammalian Brain ◽  
Transforming Growth Factor Α ◽  
Factor Α

EGF receptor tyrosine kinase inhibitors diminish transforming growth factor-α-induced pulmonary fibrosis

2008 ◽  
Vol 294 (6) ◽  
pp. L1217-L1225 ◽  
Author(s):  
William D. Hardie ◽  
Cynthia Davidson ◽  
Machiko Ikegami ◽  
George D. Leikauf ◽  
Timothy D. Le Cras ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Pulmonary Mechanics ◽  
Transforming Growth Factor Α ◽  
Egfr Activation ◽  
Factor Α

Transforming growth factor-α (TGF-α) is a ligand for the EGF receptor (EGFR). EGFR activation is associated with fibroproliferative processes in human lung disease and animal models of pulmonary fibrosis. We determined the effects of EGFR tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) on the development and progression of TGF-α-induced pulmonary fibrosis. Using a doxycycline-regulatable transgenic mouse model of lung-specific TGF-α expression, we determined effects of treatment with gefitinib and erlotinib on changes in lung histology, total lung collagen, pulmonary mechanics, pulmonary hypertension, and expression of genes associated with synthesis of ECM and vascular remodeling. Induction in the lung of TGF-α caused progressive pulmonary fibrosis over an 8-wk period. Daily administration of gefitinib or erlotinib prevented development of fibrosis, reduced accumulation of total lung collagen, prevented weight loss, and prevented changes in pulmonary mechanics. Treatment of mice with gefitinib 4 wk after the induction of TGF-α prevented further increases in and partially reversed total collagen levels and changes in pulmonary mechanics and pulmonary hypertension. Increases in expression of genes associated with synthesis of ECM as well as decreases of genes associated with vascular remodeling were also prevented or partially reversed. Administration of gefitinib or erlotinib did not cause interstitial fibrosis or increases in lavage cell counts. Administration of small molecule EGFR tyrosine kinase inhibitors prevented further increases in and partially reversed pulmonary fibrosis induced directly by EGFR activation without inducing inflammatory cell influx or additional lung injury.

scholarly journals Mammary Carcinogenesis Is Preceded by Altered Epithelial Cell Turnover in Transforming Growth Factor-α and c-myc Transgenic Mice

2006 ◽  
Vol 169 (5) ◽  
pp. 1821-1832 ◽  
Author(s):  
Teresa A. Rose-Hellekant ◽  
Kristin M. Wentworth ◽  
Sarah Nikolai ◽  
Donald W. Kundel ◽  
Eric P. Sandgren
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Transgenic Mice ◽  
Transforming Growth Factor ◽  
Mammary Carcinogenesis ◽  
Cell Turnover ◽  
Transforming Growth Factor Α ◽  
Factor Α

scholarly journals Regulation of Transforming Growth Factor α Expression in a Growth Factor-Independent Cell Line

1998 ◽  
Vol 18 (1) ◽  
pp. 303-313 ◽  
Author(s):  
Gillian M. Howell ◽  
Lisa E. Humphrey ◽  
Barry L. Ziober ◽  
Rana Awwad ◽  
Basker Periyasamy ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Line ◽  
Antisense Rna ◽  
Promoter Activity ◽  
Transforming Growth Factor ◽  
Hct116 Cell ◽  
Malignant Phenotype ◽  
Hct116 Cell Line ◽  
Transforming Growth Factor Α ◽  
Factor Α

ABSTRACT Aberrant transcriptional regulation of transforming growth factor α (TGFα) appears to be an important contributor to the malignant phenotype and the growth factor independence with which malignancy is frequently associated. However, little is known about the molecular mechanisms responsible for dysregulation of TGFα expression in the malignant phenotype. In this paper, we report on TGFα promoter regulation in the highly malignant growth factor-independent cell line HCT116. The HCT116 cell line expresses TGFα and the epidermal growth factor receptor (EGFR) but is not growth inhibited by antibodies to EGFR or TGFα. However, constitutive expression of TGFα antisense RNA in the HCT116 cell line resulted in the isolation of clones with markedly reduced TGFα mRNA and which were dependent on exogenous growth factors for proliferation. We hypothesized that if TGFα autocrine activation is the major stimulator of TGFα expression in this cell line, TGFα promoter activity should be reduced in the antisense TGFα clones in the absence of exogenous growth factor. This was the case. Moreover, transcriptional activation of the TGFα promoter was restored in an antisense-TGFα-mRNA-expressing clone which had reverted to a growth factor-independent phenotype. Using this model system, we were able to identify a 25-bp element within the TGFα promoter which conferred TGFα autoregulation to the TGFα promoter in the HCT116 cell line. In the TGFα-antisense-RNA-expressing clones, this element was activated by exogenous EGF. This 25-bp sequence contained no consensus sequences of known transcription factors so that the TGFα or EGF regulatory element within this 25-bp sequence represents a unique element. Further characterization of this 25-bp DNA sequence by deletion analysis revealed that regulation of TGFα promoter activity by this sequence is complex, as both repressors and activators bind in this region, but the overall expression of the activators is pivotal in determining the level of response to EGF or TGFα stimulation. The specific nuclear proteins binding to this region are also regulated in an autocrine-TGFα-dependent fashion and by exogenous EGF in EGF-deprived TGFα antisense clone 33. This regulation is identical to that seen in the growth factor-dependent cell line FET, which requires exogenous EGF for optimal growth. Moreover, the time response of the stimulation oftrans-acting factor binding by EGF suggests that the effect is directly due to growth factor and not mediated by changes in growth state. We conclude that this element appears to represent the major positive regulator of TGFα expression in the growth factor-independent HCT116 cell line and may represent the major site of transcriptional dysregulation of TGFα promoter activity in the growth factor-independent phenotype.

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