Publications by authors named "Danielle M Hernandez"
Article Synopsis
- Pathogenic fibrotic diseases like idiopathic pulmonary fibrosis (IPF) affect millions and have poor prognoses, with two-thirds of patients dying within 2-5 years due to limited treatment options.
- The study highlights the upregulation of IGF-1 in myofibroblasts induced by TGFβ, linking it to decreased lung function in IPF patients.
- Researchers found that TGFβ activates IGF-1 through specific signaling pathways and demonstrated that inhibiting IGF-1 receptor effectively slows lung fibrosis progression in mouse models, pointing to potential new therapeutic approaches.
Metabolic dysregulation in fibroblasts is implicated in the profibrotic actions of transforming growth factor-β (TGF-β). Here, we present evidence that hexokinase 2 (HK2) is important for mediating the fibroproliferative activity of TGF-β both in vitro and in vivo. Both Smad-dependent and Smad-independent TGF-β signaling induced HK2 accumulation in murine and human lung fibroblasts through induction of the transcription factor c-Myc.
View Article and Find Full Text PDFEvidence is provided that the fibroproliferative actions of TGF-β are dependent on a metabolic adaptation that sustains pathologic growth. Specifically, profibrotic TGF-β signaling is shown to require fatty acid synthase (FASN), an essential anabolic enzyme responsible for the de novo synthesis of fatty acids. With the use of pharmacologic and genetic approaches, we show that TGF-β-stimulated FASN expression is independent of Smad2/3 and is mediated via mammalian target of rapamycin complex 1.
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- - The study focuses on how specific receptors, TβRI and TβRII, correctly localize to the basolateral region of polarized epithelial cells, which is crucial for their physiological function.
- - Researchers discovered that a specific sequence (VxxEED) in TβRI is essential for its proper basolateral targeting, while also noting that changes to this sequence did not affect receptor internalization or signaling pathways.
- - Additionally, when the region containing the targeting sequence is included, it can redirect other receptors, like NGFR, to the correct basolateral location, showing that receptor localization is key to signaling, particularly in TGF-β pathways.
TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3).
View Article and Find Full Text PDFTGF-β plays a central role in the pathogenesis of fibroproliferative disorders. Defining the exact underlying molecular basis is therefore critical for the development of viable therapeutic strategies. Here, we show that expression of the facilitative glucose transporter 1 (GLUT1) is induced by TGF-β in fibroblast lines and primary cells and is required for the profibrotic effects of TGF-β.
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