Phenotype of Skin Dermal Mast Cells in Marfan Syndrome in Terms of Extracellular Matrix Remodeling

Introduction. Marfan syndrome (SM) is a hereditary disease caused by a mutation in FBN1 gene, leading to the synthesis of abnormal glycoprotein fibrillin 1, disturbances in the structural and regulatory properties of connective tissue, primarily, in elastic fibers. Despite the high potential of mast cells (MCs) to remodel the extracellular matrix, their pathogenetic significance in Marfan syndrome has not yet been considered. Purpose. To identify features of the population structure of mast cells in the skin of children with Marfan syndrome, including patterns of spatial architecture of intraorganic histotopography and pathogenetic significance of specific proteases in the mechanisms of remodeling of the fibrous component of the extracellular matrix of the dermis. Materials and methods. The study was performed using skin biomaterial taken between 2022 and 2023 from biopsies of the outer surface of the upper third of the shoulder in patients with Marfan syndrome, with further histochemical and immunohistochemical staining and counting of the absolute number of mast cells and other cells, the area ratio of elastic and collagen fibers, as well as determining the profile of specific mast cell proteases by multiplex staining of tryptase, chymase and carboxypeptidase A3. Results. The analysis of the MC population of the skin of children with Marfan syndrome revealed a significant increase in the size of the intraorgan population while maintaining the predominant profile of specific proteases Tryptase+Chymase+CPA3+. The histotopographic analysis showed a significant increase in the frequency of colocalization of MCs with elastic fibers, primarily with their abnormal areas, as well as with αSMA+ cells and fibroblasts. In terms of spatial architecture of distribution in the skin, MCs in hereditary pathology created multicellular clusters synchronizing cells activity in the tissue microenvironment and contributing to formation of tissue niches of profibrotic phenotype. An increase in the expression of specific proteases, TGF-β and heparin in MCs with targeted secretion of substances to abnormal areas of elastic fibers was revealed. The specific role of MCs in the remodeling of the stromal landscape of connective tissue in SM is discussed. For the first time, the issue of MCs involvement in tensometry of skin tissue microenvironment is raised. It is advisable to take into account the obtained results when treating clinical manifestations of Marfan syndrome in other pathogenetically significant structures of internal organs, including the aorta, tendons, cartilage and parenchymal organs. © 2024, Professionalnye Izdaniya. All rights reserved.