scholarly journals Deciphering the role of the Pancreatic Secretome in Covid-19 associated Multi-Organ Dysfunctions

2021 ◽  
Author(s):  
Ekta Pathak ◽  
Rajeev Mishra

Emerging evidence indicates an intricate relationship between the SARS-CoV-2 infection and Multi-Organ Dysfunctions (MODs). Here, we have investigated the role of the Secretome of the SARS-CoV-2 infected pancreas and mechanistically linked it with the multi-organ dysfunction using the scRNA-seq analysis. We found that acinar-specific PRSS2, REG3A, REG1A, SPINK1, and ductal-specific SPP1, MMP7 genes are upregulated in alpha, beta, delta, and mesenchyme cells. Using extensive documented experimental evidence, we validated the association of upregulated pancreatic Secretome with coagulation cascade, complement activation, renin angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of upregulated Secretome on multi-organ systems such as Nervous, Cardiovascular, Immune, Digestive, and Urogenital systems. In addition, we report that the secretory proteins IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF are associated with diverse diseases. Thus, suggest the role of the pancreatic Secretome in SARS-CoV-2 associated MODs.

1992 ◽  
Vol 161 (9) ◽  
pp. 561-564 ◽  
Author(s):  
R. Clarke ◽  
E. Naughten ◽  
S. Cahalane ◽  
K. O. Sullivan ◽  
P. Mathias ◽  
...  

2002 ◽  
Vol 283 (2) ◽  
pp. C396-C403 ◽  
Author(s):  
Zoltán H. Németh ◽  
Edwin A. Deitch ◽  
Qi Lu ◽  
Csaba Szabó ◽  
György Haskó

Na+/H+exchanger (NHE) activation has been documented to contribute to endothelial cell injury caused by inflammatory states. However, the role of NHEs in regulation of the endothelial cell inflammatory response has not been investigated. The present study tested the hypothesis that NHEs contribute to endothelial cell inflammation induced by endotoxin or interleukin (IL)-1β. NHE inhibition using amiloride, 5-( N-ethyl- N-isopropyl)-amiloride, and 5-( N-methyl- N-isobutyl)amiloride as well as the non-amiloride NHE inhibitors cimetidine, clonidine, and harmaline suppressed endotoxin-induced IL-8 and monocyte chemoattractant protein (MCP)-1 production by human umbilical endothelial vein cells (HUVECs). The suppressive effect of amiloride on endotoxin-induced IL-8 production was associated with a decreased accumulation of IL-8 mRNA. NHE inhibitors suppressed both inhibitory (I)κB degradation and nuclear factor (NF)-κB DNA binding, suggesting that a decrease in activation of the IκB-NF-κB system contributed to the suppression of HUVEC inflammatory response by NHE blockade. NHE inhibition decreased also the IL-1β-induced HUVEC inflammatory response, because amiloride suppressed IL-1β-induced E-selectin expression on HUVECs. These results demonstrate that maximal activation of the HUVEC inflammatory response requires a functional NHE.


2010 ◽  
Vol 56 (6) ◽  
pp. 1168-1174 ◽  
Author(s):  
Ryan J. Goldberg ◽  
Takahiko Nakagawa ◽  
Richard J. Johnson ◽  
Joshua M. Thurman

1978 ◽  
Vol 39 (02) ◽  
pp. 312-321 ◽  
Author(s):  
Laurence A Harker ◽  
Russell Ross ◽  
John A Glomset

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