Researchers showed that smooth muscle cell (SMC)-specific knockout of the Pdgfrb gene, which encodes platelet-derived growth factor receptor beta (PDGFRβ), in Apoe−/− mice fed a Western diet for 18 weeks resulted in brachiocephalic artery lesions nearly devoid of SMCs but with no changes in lesion size, remodelling or indices of stability, including the percentage of ACTA2+ fibrous cap cells.
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Newman, A. A. C., Serbulea, V., Baylis, R. A., Shankman, L. S., Bradley, X., Alencar, G. F., Owsiany, K., Deaton, R. A., Karnewar, S., Shamsuzzaman, S., Salamon, A., Reddy, M. S., Guo, L., Finn, A., Virmani, R., Cherepanova, O. A., & Owens, G. K. (2021). Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms. Nature Metabolism, 3(2), 166–181. https://doi.org/10.1038/s42255-020-00338-8 Cite
Scientists used multiple colorectal cancer (CRC) cell lines to investigate the growth-inhibitory effect of crenolanib and its effect in combination with other cytotoxic agents. Primary cultures of patient-derived organoids, a model that reflects the heterogeneity of clinical CRC, were used to further validate the effects of crenolanib.
[Molecular Cancer Research]
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Scientists tested whether anaplastic lymphoma kinase AL2 (ALKAL2) ligand could potentiate neuroblastoma progression in the absence of ALK mutation
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Borenäs, M., Umapathy, G., Lai, W.-Y., Lind, D. E., Witek, B., Guan, J., Mendoza-Garcia, P., Masudi, T., Claeys, A., Chuang, T.-P., El Wakil, A., Arefin, B., Fransson, S., Koster, J., Johansson, M., Gaarder, J., Van den Eynden, J., Hallberg, B., & Palmer, R. H. (2021). ALK ligand ALKAL2 potentiates MYCN-driven neuroblastoma in the absence of ALK mutation. The EMBO Journal, n/a(n/a), e105784. https://doi.org/10.15252/embj.2020105784 Cite
Scientists examine the efficacy of a human bone marrow-derived MSC therapy delivered at three or 30 hours in ameliorating radiation-induced hematopoietic syndrome and show that pancytopenia persists despite MSC therapy.
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Diaz, M. F., Horton, P. lina D., Dumbali, S. P., Kumar, A., Livingston, M., Skibber, M. A., Mohammadalipour, A., Gill, B. S., Zhang, S., Cox, C. S., & Wenzel, P. L. (2020). Bone marrow stromal cell therapy improves survival after radiation injury but does not restore endogenous hematopoiesis. Scientific Reports, 10(1), 22211. https://doi.org/10.1038/s41598-020-79278-y Cite
Researchers investigated whether platelet‑derived growth factor (PDGF) affects the proliferation and migration of pulmonary arterial smooth muscle cells by regulating nuclear factor of activated T cell (NFAT), and to study the pathogenesis of pulmonary arterial hypertension.
[Molecular Medicine Reports]
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Proteomic analyses of human angiogenesis-related factors produced by human adipose tissue-derived stromal/stem cells (hADSCs) showed that both pro- and anti-angiogenic factors were produced by hADSCs in vitro, but only those related to vessel maturation were detectable in vivo.
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Menezes, K., Rosa, B. G., Freitas, C., da Cruz, A. S., de Siqueira Santos, R., Nascimento, M. A., Alves, D. V. L., Bonamino, M., Rossi, M. I., Borojevic, R., & Coelho-Sampaio, T. (2020). Human mesenchymal stromal/stem cells recruit resident pericytes and induce blood vessels maturation to repair experimental spinal cord injury in rats. Scientific Reports, 10(1), 19604. https://doi.org/10.1038/s41598-020-76290-0 Cite
Employing CRISPR/Cas9 gene editing to disrupt the Pdgfra gene in two different murine cell lines, scientists showed that in addition to the widely accepted function for Platelet Derived Growth Factor Receptor (PDGFR) -beta in Circular Dorsal Ruffles (CDRs) formation, PDGFR-alpha is also clearly capable of eliciting CDRs.
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The CARD8 mRNA was knocked-down in HUVECs in vitro, followed by quantitative RT-PCR analysis and OLINK Proteomics. Endothelial and smooth muscle cells in arterial tissue expressed CARD8 and CARD8 correlated with vWF, CD163 and the expression of inflammatory genes, such as CXCL1, CXCL6 and PDGF-A in plaque.
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Paramel, G. V., Karadimou, G., Eremo, A. G., Ljungberg, L. U., Hedin, U., Olofsson, P. S., Folkersen, L., Berne, G. P., Sirsjö, A., & Fransén, K. (2020). Expression of CARD8 in human atherosclerosis and its regulation of inflammatory proteins in human endothelial cells. Scientific Reports, 10(1), 19108. https://doi.org/10.1038/s41598-020-73600-4 Cite
Gene set enrichment analysis and additional assays confirmed that ETV5 could promote angiogenesis by inducing the secretion of another tumor angiogenesis factor (CCL2) in CRC cells to facilitate Bevacizumab resistance.
[Cell Death & Disease]
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All-trans retinoic acid (ATRA) could repress the PDGF-bb-induced excessive proliferation and migration of human umbilical vein smooth muscle cells, which was mediated by Rb-E2F dependent cell cycle inhibition.
[Cardiovascular Drugs and Therapy]
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Yu, Y., Wang, Y., Fei, X., Song, Z., Xie, F., Yang, F., Liu, X., Xu, Z., & Wang, G. (2020). All-Trans Retinoic Acid Prevented Vein Grafts Stenosis by Inhibiting Rb-E2F Mediated Cell Cycle Progression and KLF5-RARα Interaction in Human Vein Smooth Muscle Cells. Cardiovascular Drugs and Therapy. https://doi.org/10.1007/s10557-020-07089-4 Cite
Researchers investigated the expression of extracellular matrix by dermal fibroblast mimicking fibrotic skin diseases as systemic sclerosis using clinically validated biomarkers.
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Juhl, P., Bondesen, S., Hawkins, C. L., Karsdal, M. A., Bay-Jensen, A.-C., Davies, M. J., & Siebuhr, A. S. (2020). Dermal fibroblasts have different extracellular matrix profiles induced by TGF-β, PDGF and IL-6 in a model for skin fibrosis. Scientific Reports, 10(1), 17300. https://doi.org/10.1038/s41598-020-74179-6 Cite