Signal transducer and activator of transcription 1-alpha/beta (Transcription factor ISGF-3 components p91/p84)
развернуть
Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2.
The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 mRNA than any other organ. By immunohistochemistry, duodenum, kidney and testis showed strong signals, whereas the signal was weak in the respiratory tract. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in the renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene as well as a new putative short form of ACE2. These include several interferon-stimulated response elements sites for STAT1, IRF8, and IRF9. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.
MeSH Terms
- Aging
- Angiotensin-Converting Enzyme 2
- Betacoronavirus
- Binding Sites
- COVID-19
- Carrier Proteins
- Computational Biology
- Coronavirus Infections
- Female
- Gene Expression Regulation, Enzymologic
- Gene Ontology
- Humans
- Interferons
- Lung
- Male
- Metalloproteases
- Neovascularization, Physiologic
- Organ Specificity
- Pandemics
- Peptidyl-Dipeptidase A
- Pneumonia, Viral
- Promoter Regions, Genetic
- RNA, Messenger
- Receptors, Virus
- Renin-Angiotensin System
- SARS-CoV-2
- Sex Characteristics
- Single-Cell Analysis
- Transcription Factors
- Transcription Initiation Site
- Virus Attachment
{{medline-entry
|title=STAT1-p53-p21axis-dependent stress-induced progression of chronic nephrosis in adriamycin-induced mouse model.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32953802
|abstract=Chronic nephrosis (CN) is an aging-related disease with high mortality. Signal transduction and transcriptional activator 1 (STAT1) protein promotes senescence in human glomerular mesangial cells (HMCs), but whether it affects the progression of adriamycin (ADR)-induced CN [i]in vivo[/i] remains unclear. We established an ADR-induced CN mouse model that was completed in wild-type (wt) mice by a single intravenous injection of 10 mg/kg ADR for 2 or 4 weeks. Clinical indexes in each group were determined. Hematoxylin and eosin staining (H