Role of GILZ in the Kidney and the Cardiovascular System: Relevance to Cardiorenal Complications of COVID-19

Glucocorticoids are extensively used for a variety of conditions, including those associated with dysregulation of immune and inflammatory responses as primary etiopathogenic factors. Indeed, the proinflammatory cytokine storm of coronavirus disease 2019 (COVID-19) is the latest condition for which the use of a glucocorticoid has been advocated. Recognition of serious adverse effects of glucocorticoids has led to research aimed at unraveling molecular basis by which they impact immune and inflammatory events with the ultimate objective of devising novel therapies to circumvent glucocorticoids-related adverse outcomes. Consequently, glucocorticoid-induced leucine zipper (GILZ) protein was discovered and is increasingly recognized as the pivotal regulator of the effects of glucocorticoids on immune and inflammatory responses. Importantly, the advent of GILZ-based options raises the prospect of their eventual therapeutic use for a variety of conditions accompanied with dysregulation of immune and inflammatory responses and associated target organ complications. Thus, the objective of this minireview is to describe our current understanding of the role of GILZ in the cardiovascular system and the kidney along with outcome of GILZ-based interventions on associated disorders. This information is also of relevance for emerging complications of COVID-19. SIGNIFICANCE STATEMENT: Glucocorticoid-induced leucine zipper (GILZ) was initially discovered as the pivotal mediator of immune regulatory/suppressive effects of glucocorticoids. Since the use of glucocorticoids is associated with serious adverse effects, GILZ-based formulations could offer therapeutic advantages. Thus, this minireview will describe our current understanding of the role of GILZ in the kidney and the cardiovascular system, which is of relevance and significance for pathologies affecting them, including the multiorgan complications of coronavirus disease 2019.