Potential Involvement of NHE1 in COVID‐19 Related Pulmonary Damage

Abstract

In some moderate and severe COVID‐19 infections lung scarring similar to fibrosis have been observed in survivors, many of which have persistent functional and radiographic abnormalities at the initial follow‐up suggesting a possible shared pathobiology between fibrotic lung disease and COVID‐19‐ lung disease. Fibrosis is an inflammatory response to pulmonary infections that activates fibroblasts and produces excessive extracellular matrix proteins that stiffen cells, leading to reduction in lung capacity and breathing deficiency. Several factors involved in the “cytokine storm” also are pre‐fibrotic leading to the advanced disease. This includes interleukin 6 and others. The focus of this study is on sodium hydrogen exchanger isoform 1 (NHE1) that plays a key role in intracellular pH regulation and cell movement and its effect on fibrosis development. Both cytokines IL‐1 and IL‐6 are used to show one measure of cell restructuring and stiffness by measuring stress fiber formation. To examine the role of NHE1 in fibroblast response, both IL‐1 and IL‐6 cells were treated with proinflammatory cytokines in the presence and absence of NHE1 inhibitor (EIPA). This study will provide an initial insight to the relationship between NHE1 and proinflammatory response for future experiments.