Bibliographic Details
| Title: |
Role of the Senescence-Associated Factor Dipeptidyl Peptidase 4 in the Pathogenesis of SARS-CoV-2 Infection. |
| Authors: |
Deinhardt-Emmer, Stefanie, Deshpande, Sharvari, Kitazawa, Koji, Herman, Allison B., Bons, Joanna, Rose, Jacob P., Kumar, Prasanna Ashok, Anerillas, Carlos, Neri, Francesco, Ciotlos, Serban, Perez, Kevin, Köse-Vogel, Nilay, Häder, Antje, Abdelmohsen, Kotb, Löffler, Bettina, Gorospe, Myriam, Desprez, Pierre-Yves, Melov, Simon, Furman, David, Schilling, Birgit |
| Source: |
Aging & Disease; Jun2024, Vol. 15 Issue 3, p1398-1415, 18p |
| Subject Terms: |
SARS-CoV-2, PEPTIDASE, PROTEIN expression |
| Abstract: |
During cellular senescence, persistent growth arrest and changes in protein expression programs are accompanied by a senescence-associated secretory phenotype (SASP). In this study, we detected the upregulation of the SASP-related protein dipeptidyl peptidase 4 (DDP4) in human primary lung cells rendered senescent by exposure to ionizing radiation. DPP4 is an exopeptidase that plays a crucial role in the cleavage of various proteins, resulting in the loss of N-terminal dipeptides and proinflammatory effects. Interestingly, our data revealed an association between severe coronavirus disease 2019 (COVID-19) and DDP4, namely that DPP4 levels increased in the plasma of patients with COVID-19 and were correlated with age and disease progression. Although we could not determine the direct effect of DDP4 on viral replication, mechanistic studies in cell culture revealed a negative impact on the expression of the tight junction protein zonula occludens-1 (ZO-1), which contributes to epithelial barrier function. Mass spectrometry analysis indicated that DPP4 overexpressing cells exhibited a decrease in ZO-1 and increased expression of pro-inflammatory cytokines and chemokines. By investigating the effect of DPP4 on the barrier function of human primary cells, we detected an increase in ZO-1 using DPP4 inhibitors. These results provide an important contribution to our understanding of DPP4 in the context of senescence, suggesting that DPP4 plays a major role as part of the SASP. Our results provide evidence that cellular senescence, a hallmark of aging, has an important impact on respiratory infections. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
