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10.3390/cells11010022

http://scihub22266oqcxt.onion/10.3390/cells11010022
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35011584!8750694!35011584
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suck abstract from ncbi


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pmid35011584      Cells 2021 ; 11 (1): ä
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  • Role of Human Antigen R (HuR) in the Regulation of Pulmonary ACE2 Expression #MMPMID35011584
  • Aloufi N; Haidar Z; Ding J; Nair P; Benedetti A; Eidelman DH; Gallouzi IE; Di Marco S; Hussain SN; Baglole CJ
  • Cells 2021[Dec]; 11 (1): ä PMID35011584show ga
  • Patients with COPD may be at an increased risk for severe illness from COVID-19 because of ACE2 upregulation, the entry receptor for SARS-CoV-2. Chronic exposure to cigarette smoke, the main risk factor for COPD, increases pulmonary ACE2. How ACE2 expression is controlled is not known but may involve HuR, an RNA binding protein that increases protein expression by stabilizing mRNA. We hypothesized that HuR would increase ACE2 protein expression. We analyzed scRNA-seq data to profile ELAVL1 expression in distinct respiratory cell populations in COVID-19 and COPD patients. HuR expression and cellular localization was evaluated in COPD lung tissue by multiplex immunohistochemistry and in human lung cells by imaging flow cytometry. The regulation of ACE2 expression was evaluated using siRNA-mediated knockdown of HuR. There is a significant positive correlation between ELAVL1 and ACE2 in COPD cells. HuR cytoplasmic localization is higher in smoker and COPD lung tissue; there were also higher levels of cleaved HuR (CP-1). HuR binds to ACE2 mRNA but knockdown of HuR does not change ACE2 protein levels in primary human lung fibroblasts (HLFs). Our work is the first to investigate the association between ACE2 and HuR. Further investigation is needed to understand the mechanistic underpinning behind the regulation of ACE2 expression.
  • |*Gene Expression Regulation[MESH]
  • |Aged[MESH]
  • |Angiotensin-Converting Enzyme 2/*genetics/metabolism[MESH]
  • |COVID-19/*genetics/metabolism/virology[MESH]
  • |Cells, Cultured[MESH]
  • |ELAV-Like Protein 1/*genetics/metabolism[MESH]
  • |Female[MESH]
  • |Fibroblasts/metabolism[MESH]
  • |Gene Expression Profiling/methods[MESH]
  • |Humans[MESH]
  • |Lung/*metabolism/pathology/virology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Pulmonary Disease, Chronic Obstructive/genetics/metabolism/virology[MESH]
  • |RNA Interference[MESH]
  • |RNA-Seq/methods[MESH]
  • |SARS-CoV-2/physiology[MESH]


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