Abstract
Increasing evidence demonstrated that the expression of Angiotensin I-Converting Enzyme type 2 (ACE2) is a necessary step for SARS-CoV-2 infection permissiveness. In light of the recent data highlighting an association between COVID-19 and diabetes, a detailed analysis aimed at evaluating ACE2 expression pattern distribution in human pancreas is still lacking. Here, we took advantage of INNODIA network EUnPOD biobank collection to thoroughly analyze ACE2, both at mRNA and protein level, in multiple human pancreatic tissues and using several methodologies. Using multiple reagents and antibodies, we showed that ACE2 is expressed in human pancreatic islets, where it is preferentially expressed in subsets of insulin producing β-cells. ACE2 is also highly expressed in pancreas microvasculature pericytes and moderately expressed in rare scattered ductal cells. By using different ACE2 antibodies we showed that a recently described short-ACE2 isoform is also prevalently expressed in human β-cells. Finally, using RT-qPCR, RNA-seq and High-Content imaging screening analysis, we demonstrated that pro-inflammatory cytokines, but not palmitate, increase ACE2 expression in the β-cell line EndoC-βH1 and in primary human pancreatic islets. Taken together, our data indicate a potential link between SARS-CoV-2 and diabetes through putative infection of pancreatic microvasculature and/or ductal cells and/or through direct β-cell virus tropism.
Highlights
The expression of molecules that act as receptors for viruses determines tissue-specific tropism
To determine the Angiotensin I-Converting Enzyme type 2 (ACE2) protein expression pattern in human pancreatic tissue, we first performed a colorimetric immunohistochemistry analysis to detect ACE2 on formalin-fixed paraffin embedded (FFPE) pancreatic sections obtained from seven (n = 7) adult non-diabetic multiorgan donors collected by the INNODIA EUnPOD biobank (Table S1)
The observed ACE2 expression in the islets was lower than the expression observed in the microvasculature, the latter representing the main site for ACE2 expression in the pancreas
Summary
The expression of molecules that act as receptors for viruses determines tissue-specific tropism. SARS-coronavirus 2 (SARSCoV-2), that leads to the respiratory illness coronavirus disease 2019 (COVID-19), uses its surface envelope Spike glycoprotein (S-protein) to interact and gain access to host cells through the Angiotensin-I converting enzyme-2 (ACE2) receptor. Sprotein-ACE2 binding is the key determinant for virus entry, propagation, and transmissibility of COVID-19-related disease [1, 2]. SARS-CoV-2 does not enter cells that do not express ACE2 and does not use other coronavirus receptors, such as aminopeptidase N (APN) and dipeptidyl peptidase 4 (DPP4), being fully dependent on ACE2 presence in host cells [5]. SARS-CoV-2 mainly targets cells of the nasal, bronchial, and lung epithelium, causing respiratory-related symptoms; growing evidence shows that other tissues can be infected
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