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1.
ACS Biomater Sci Eng ; 7(8): 3487-3502, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1319013

ABSTRACT

The coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, SARS-CoV-2, affects tissues from different body systems but mostly the respiratory system, and the damage evoked in the lungs may occasionally result in severe respiratory complications and eventually lead to death. Studies of human respiratory infections have been limited by the scarcity of functional models that mimic in vivo physiology and pathophysiology. In the last decades, organoid models have emerged as potential research tools due to the possibility of reproducing in vivo tissue in culture. Despite being studied for over one year, there is still no effective treatment against COVID-19, and investigations using pulmonary tissue and possible therapeutics are still very limited. Thus, human lung organoids can provide robust support to simulate SARS-CoV-2 infection and replication and aid in a better understanding of their effects in human tissue. The present review describes methodological aspects of different protocols to develop airway and alveoli organoids, which have a promising perspective to further investigate COVID-19.


Subject(s)
COVID-19 , Organoids , Humans , Lung , Pulmonary Alveoli , SARS-CoV-2
2.
Mol Cell Endocrinol ; 515: 110917, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-661768

ABSTRACT

Obesity patients are more susceptible to develop COVID-19 severe outcome due to the role of angiotensin-converting enzyme 2 (ACE2) in the viral infection. ACE2 is regulated in the human cells by different genes associated with increased (TLR3, HAT1, HDAC2, KDM5B, SIRT1, RAB1A, FURIN and ADAM10) or decreased (TRIB3) virus replication. RNA-seq data revealed 14857 genes expressed in human subcutaneous adipocytes, including genes mentioned above. Irisin treatment increased by 3-fold the levels of TRIB3 transcript and decreased the levels of other genes. The decrease in FURIN and ADAM10 expression enriched diverse biological processes, including extracellular structure organization. Our results, in human subcutaneous adipocytes cell culture, indicate a positive effect of irisin on the expression of multiple genes related to viral infection by SARS-CoV-2; furthermore, translatable for other tissues and organs targeted by the novel coronavirus and present, thus, promising approaches for the treatment of COVID-19 infection as therapeutic strategy to decrease ACE2 regulatory genes.


Subject(s)
Adipocytes/drug effects , Fibronectins/pharmacology , Gene Expression Regulation/drug effects , ADAM10 Protein/genetics , ADAM10 Protein/metabolism , Adipocytes/cytology , Adipocytes/metabolism , Amyloid Precursor Protein Secretases/genetics , Amyloid Precursor Protein Secretases/metabolism , Angiotensin-Converting Enzyme 2 , Betacoronavirus/genetics , Betacoronavirus/metabolism , COVID-19 , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cells, Cultured , Coronavirus Infections/virology , Fibronectins/genetics , Fibronectins/metabolism , Furin/genetics , Furin/metabolism , Gene Ontology , Histone Acetyltransferases/genetics , Histone Acetyltransferases/metabolism , Histone Deacetylase 2/genetics , Histone Deacetylase 2/metabolism , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Models, Biological , Molecular Sequence Annotation , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Obesity/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , SARS-CoV-2 , Signal Transduction , Sirtuin 1/genetics , Sirtuin 1/metabolism , Toll-Like Receptor 3/genetics , Toll-Like Receptor 3/metabolism , rab1 GTP-Binding Proteins/genetics , rab1 GTP-Binding Proteins/metabolism
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