The role of epidermal growth factor receptor (EGFR) signaling in SARS coronavirus-induced pulmonary fibrosis

Abstract

Many survivors of the 2003 outbreak of severe acute respiratory syndrome (SARS) developed residual pulmonary fibrosis with increased severity seen in older patients. Autopsies of patients that died from SARS also showed fibrosis to varying extents. Pulmonary fibrosis can be occasionally seen as a consequence to several respiratory viral infections but is much more common after a SARS coronavirus (SARS-CoV) infection. Given the threat of future outbreaks of severe coronavirus disease, including Middle East respiratory syndrome (MERS), it is important to understand the mechanisms responsible for pulmonary fibrosis, so as to support the development of therapeutic countermeasures and mitigate sequelae of infection. In this article, we summarize pulmonary fibrotic changes observed after a SARS-CoV infection, discuss the extent to which other respiratory viruses induce fibrosis, describe available animal models to study the development of SARS-CoV induced fibrosis and review evidence that pulmonary fibrosis is caused by a hyperactive host response to lung injury mediated by epidermal growth factor receptor (EGFR) signaling. We summarize work from our group and others indicating that inhibiting EGFR signaling may prevent an excessive fibrotic response to SARS-CoV and other respiratory viral infections and propose directions for future research.

Transmission and epidemiological characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19): preliminary evidence obtained in comparison with 2003-SARS

“…In 2002, a case of SARS appeared in Guangdong Province, China, and then spread to Southeast Asia and all of the world [6] . The SARS outbreak comprehensively All rights reserved.…”

“…Age and comorbidities (such as diabetes or heart disease) are independent predictors of poor SARS-CoV and MERS-CoV outcomes. The spread of SARS-CoV and MERS-CoV occurred to a large extent through super-transmission events [6][7] .…”

Urgent avenues in the treatment of COVID-19: Targeting downstream inflammation to prevent catastrophic syndrome

“…It is known that TGF-␤ is an antiinflammatory cytokine that can induce fibrogenesis. More recently, it has been suggested that pulmonary fibrosis in SARS-CoV is caused by a hyperactive host response to lung injury mediated by epidermal growth factor receptor (EGFR) signalling [20]. Inhibiting EGFR signalling, by the use of tyrosine kinase inhibitors like nintedanib, a drug licensed for idiopathic lung fibrosis, seems promising for interstitial lung disease in systemic sclerosis [21], and might also be useful for COVID-19.…”

Novel Pyrimidines as Multitarget Protein Tyrosine Kinase Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)

“…Signaling through the IL‐15 receptor is known to be important in the development . Recent studies showed that JAK‐STAT signaling play an important role in the pathogenesis of pulmonary fibrosis, and thus inhibition JAK‐STAT signaling in fibroblasts may be effective in the treatment of fibrosis . Bruton's tyrosine kinase (BTK) is a type of kinase protein expressed in B lymphocytes and T cells .…”

“…[17,18] Recent studies showed that JAK-STAT signaling play an important role in the pathogenesis of pulmonary fibrosis, and thus inhibition JAK-STAT signaling in fibroblasts may be effective in the treatment of fibrosis. [19][20][21][22] Bruton's tyrosine kinase (BTK) is a type of kinase protein expressed in B lymphocytes and T cells. [23] BTK deficiency in humans is associated with reduction in TNF-α production by activated monocytes.…”