Skin mast cells in Marfan syndrome: specific emphasis on connective tissue remodeling

Abstract

Marfan syndrome (MFS) is a hereditary condition accompanied by disorders in the structural and regulatory properties of the connective tissue, including elastic bers, due to a mutation in the FBN1 gene and the synthesis of abnormal brillin 1 glycoprotein. Despite the high potential of mast cells (MCs) to remodel the extracellular matrix (ECM), their pathogenetic signi cance in MFS has not been consideredyet. An analysis of the skin MC population in children with Marfan syndrome revealed a considerably increased number of intraorganic populations with preservation of the speci c protease Tryptase + Chymase + CPA3 + pro le typical of the skin. The features of the MC histotopography phenotype in MFS consisted of closer colocalization with elastic bers, smooth muscle cells and broblasts. MCs formed many intradermal clusters that synchronized the activity of cell functions in the stromal landscape of the tissue microenvironment with the help of spatial architectonics, including the formation of cell chains and the creation of brous niches. In MCs, the expression of speci c proteases, TGF-β and heparin increased with targeted secretion of biologically active substances to the dermal elastic bers, which, in MFS, had speci c structural features, including abnormal variability in thickness along the entire length, alternation of thickened and thinned areas, and uneven surface topography. The paper discusses the potential role of MCs in strain analysis (tensometry) of the tissue microenvironment in MFS. Thus, quantitative and qualitative rearrangements of the skin MC population in MFS are aimed at altering the stromal landscape of the connective tissue. The results obtained should be taken into account when managing clinical signs of MFS manifested in other pathogenetically critical structures of internal organs, including the aorta, tendons, cartilage and parenchymal organs.