Translational Pharmacology of an Inhaled Small Molecule αvβ6 Integrin Inhibitor for Idiopathic Pulmonary Fibrosis

Scientists report that GSK3008348 bound to αvβ6 with high affinity in human idiopathic pulmonary fibrosis lung and reduced downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induced rapid internalization and lysosomal degradation of the αvβ6 integrin.
[Nature Communications]
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Circadian Dysregulation of the TGFβ/SMAD4 Pathway Modulates Metastatic Properties and Cell Fate Decisions in Pancreatic Cancer Cells

Scientists used an in vitro pancreatic ductal adenocarcinoma model of SMAD4 positive and negative cells to investigate the interplay between circadian rhythms, the TGFβ canonical signaling pathway and its impact on tumor malignancy.
[iScience]
Li, Y., Basti, A., Yalçin, M., & Relógio, A. (2020). Circadian dysregulation of the TGFβ/SMAD4 pathway modulates metastatic properties and cell fate decisions in pancreatic cancer cells. IScience, 0(0). https://doi.org/10.1016/j.isci.2020.101551 Cite
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Impact of Sustained Transforming Growth Factor-β Receptor Inhibition on Chromatin Accessibility and Gene Expression in Cultured Human Endometrial MSC

Researchers combined RNA-seq and ATAC-seq to study the impact of sustained transforming growth factor-β receptor inhibition on gene expression and chromatin architecture of endometrial mesenchymal stem cells.
[Frontiers in Cell and Developmental Biology]
Lucciola, R., Vrljicak, P., Gurung, S., Filby, C., Darzi, S., Muter, J., Ott, S., Brosens, J. J., & Gargett, C. E. (2020). Impact of Sustained Transforming Growth Factor-β Receptor Inhibition on Chromatin Accessibility and Gene Expression in Cultured Human Endometrial MSC. Frontiers in Cell and Developmental Biology, 8. https://doi.org/10.3389/fcell.2020.567610 Cite
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It Takes Two to Tango: Endothelial TGFβ/BMP Signaling Crosstalk with Mechanobiology

Investigators summarize the current literature on crosstalk mechanisms between biochemical cues elicited by TGFβ/bone morphogenic protein growth factors and mechanical cues, as shear stress or matrix stiffness that collectively orchestrated endothelial function.
[Cells]
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Regulation of Epithelial-Mesenchymal Transition and Organoid Morphogenesis by a Novel TGFβ-TCF7L2 Isoform-Specific Signaling Pathway

Researchers found that the TCF7L2 E-isoforms maintained, whereas the M and S isoforms disrupted morphogenesis of 3D-epithelial cell-derived organoids via regulation of epithelial-mesenchymal transition.
[Cell Death & Disease]
Karve, K., Netherton, S., Deng, L., Bonni, A., & Bonni, S. (2020). Regulation of epithelial-mesenchymal transition and organoid morphogenesis by a novel TGFβ-TCF7L2 isoform-specific signaling pathway. Cell Death & Disease, 11(8), 1–20. https://doi.org/10.1038/s41419-020-02905-z Cite
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Micro-Environmental Sensing by Bone Marrow Stroma Identifies IL-6 and TGFβ1 as Regulators of Hematopoietic Aging

Researchers used bone marrow stromal cells as sensors of age-associated changes to the bone marrow microenvironment, and observed up-regulation of IL-6 and TGFβ signaling-induced gene expression in aged bone marrow stroma.
[Nature Communications]
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Micro-Environmental Sensing by Bone Marrow Stroma Identifies IL-6 and TGFβ1 as Regulators of Hematopoietic Aging

Inhibition of TGFβ signaling led to reversal of age-associated hematopoietic stem cell (HSC) platelet lineage bias, increased generation of lymphoid progenitors and rebalanced HSC lineage output in transplantation assays.
[Nature Communications]
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USP10 Targeted Self-Deliverable siRNA to Prevent Scarring in the Cornea

Investigators tested if knockdown of USP10 with a USP10-targeting sdRNA reduced scarring after wounding a rabbit cornea in vivo.
[Molecular Therapy-Nucleic Acids]
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TGFβ Biology in Cancer Progression and Immunotherapy

The authors introduce the mechanisms underlying TGFβ signaling in tumors and their microenvironment and discuss approaches to inhibit these signaling mechanisms as well as the use of these approaches in cancer immunotherapies and their potential adverse effects.
[Nature Reviews Clinical Oncology]
Derynck, R., Turley, S. J., & Akhurst, R. J. (2020). TGFβ biology in cancer progression and immunotherapy. Nature Reviews Clinical Oncology, 1–26. https://doi.org/10.1038/s41571-020-0403-1 Cite
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TGF-β Regulates Sca-1 Expression and Plasticity of Pre-Neoplastic Mammary Epithelial Stem Cells

Scientists provided evidence that TGF-β disrupted the lineage commitment and promoted the accumulation of tumor-initiating cells in pre-neoplastic cells.
[Scientific Reports]
Remšík, J., Pícková, M., Vacek, O., Fedr, R., Binó, L., Hampl, A., & Souček, K. (2020). TGF-β regulates Sca-1 expression and plasticity of pre-neoplastic mammary epithelial stem cells. Scientific Reports, 10(1), 11396. https://doi.org/10.1038/s41598-020-67827-4 Cite
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miR-146b-5p Suppresses the Malignancy of GSC/MSC Fusion Cells by Targeting SMARCA5

miR-146b-5p was downregulated in glioma stem-like cell/mesenchymal stem cell fusion cells, and its overexpression suppressed proliferation, migration and invasion by the fusion cells.
[Aging]
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