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10.1016/j.ajpath.2021.04.006

http://scihub22266oqcxt.onion/10.1016/j.ajpath.2021.04.006
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33894177!8059259!33894177
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suck abstract from ncbi


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pmid33894177      Am+J+Pathol 2021 ; 191 (7): 1193-1208
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  • Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators #MMPMID33894177
  • O'Hare M; Amarnani D; Whitmore HAB; An M; Marino C; Ramos L; Delgado-Tirado S; Hu X; Chmielewska N; Chandrahas A; Fitzek A; Heinrich F; Steurer S; Ondruschka B; Glatzel M; Krasemann S; Sepulveda-Falla D; Lagares D; Pedron J; Bushweller JH; Liu P; Arboleda-Velasquez JF; Kim LA
  • Am J Pathol 2021[Jul]; 191 (7): 1193-1208 PMID33894177show ga
  • Pulmonary fibrosis (PF) can arise from unknown causes, as in idiopathic PF, or as a consequence of infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current treatments for PF slow, but do not stop, disease progression. We report that treatment with a runt-related transcription factor 1 (RUNX1) inhibitor (Ro24-7429), previously found to be safe, although ineffective, as a Tat inhibitor in patients with HIV, robustly ameliorates lung fibrosis and inflammation in the bleomycin-induced PF mouse model. RUNX1 inhibition blunted fundamental mechanisms downstream pathologic mediators of fibrosis and inflammation, including transforming growth factor-beta1 and tumor necrosis factor-alpha, in cultured lung epithelial cells, fibroblasts, and vascular endothelial cells, indicating pleiotropic effects. RUNX1 inhibition also reduced the expression of angiotensin-converting enzyme 2 and FES Upstream Region (FURIN), host proteins critical for SARS-CoV-2 infection, in mice and in vitro. A subset of human lungs with SARS-CoV-2 infection overexpress RUNX1. These data suggest that RUNX1 inhibition via repurposing of Ro24-7429 may be beneficial for PF and to battle SARS-CoV-2, by reducing expression of viral mediators and by preventing respiratory complications.
  • |Angiotensin-Converting Enzyme 2/*metabolism[MESH]
  • |Animals[MESH]
  • |Bleomycin[MESH]
  • |COVID-19/*metabolism[MESH]
  • |Cells, Cultured[MESH]
  • |Core Binding Factor Alpha 2 Subunit/*antagonists & inhibitors[MESH]
  • |Disease Models, Animal[MESH]
  • |Epithelial Cells/drug effects/metabolism[MESH]
  • |Female[MESH]
  • |Furin/*metabolism[MESH]
  • |Lung/*drug effects/metabolism/pathology[MESH]
  • |Male[MESH]
  • |Mice[MESH]
  • |Pulmonary Fibrosis/chemically induced/*drug therapy/pathology[MESH]


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