Research Grants 19/12718-0 - Sepse, Intestinos - BV FAPESP
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Semaphorins in sepsis: role on the intestinal epithelial barrier dysfunction?

Abstract

Sepsis and multiple organ dysfunction consist of a public health issue, with high costs on the health systems, and currently comprise the main cause of mortality in intensive care units. The intestine is a severely affected organ in sepsis, whose dysfunction includes dysmotility, decreased absorptive capacity and loss of the mucosal barrier. The structural damages on the junctional complexes of the intestinal epithelium promote paracellular hyperpermeability and the passage of microbial antigens derived from the microbiota. The semaphorins (Sema) compose a family of proteins, initially described as attractive and repulsive signals for the axonal growth in the embryonic period. However, Semas exert protective effects on experimental models of sepsis in adults, possibly modulating the function of immune cells. Receptors that recognize Semas, plexins and neuropilins, are expressed in the gut mucosa, despite their roles in the maintenance of the integrity of the intestinal epithelial barrier under physiological and pathophysiological conditions are still unknown. Initially, the present study aims to evaluate the circulating concentrations of the class III Semas in a murine model of polymicrobial sepsis. In addition, those proteins with altered concentrations will guide the subsequent experiments of the intestinal epithelial barrier dysfunction using experimental models in vivo and in vitro (3D culture of intestinal organoids). In particular, the present study will investigate the direct action of Semas on the intestinal epithelial cells and also their possible indirect action in modulating the inflammatory response. Our hypothesis is that changes in the secretion profile of class III semaphorins during sepsis may be directly related to the modulation of the inflammatory response, paracellular permeability and integrity of the mucosal barrier. (AU)

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VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

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