Extracellular matrix and vascular dynamics in the kidney of a murine model for Marfan syndrome

Abstract

Fibrillin-1 is a pivotal structural component of the kidney’s glomerulus and peritubular tissue. Mutations in the fibrillin-1 gene result in Marfan syndrome (MFS), an autosomal dominant disease of the connective tissue. Although the kidney is not considered a classically affected organ in MFS, several case reports describe glomerular disease in patients. Therefore, this study aimed to characterize the kidney in the mgΔlpn-mouse model of MFS. Affected animals presented a significant reduction of glomerulus, glomerulus-capillary, and urinary space, and a significant reduction of fibrillin-1 and fibronectin in the glomerulus. Transmission electron microscopy and 3D-ultrastructure analysis revealed decreased amounts of microfibrils which also appeared fragmented in the MFS mice. Increased collagen fibers types I and III, MMP-9, and α-actin were also observed in affected animals, suggesting a tissue-remodeling process in the kidney. Video microscopy analysis showed an increase of microvessel distribution coupled with reduction of blood-flow velocity, while ultrasound flow analysis revealed significantly lower blood flow in the kidney artery and vein of the MFS mice. The structural and hemodynamic changes of the kidney indicate the presence of kidney remodeling and vascular resistance in this MFS model. Both processes are associated with hypertension which is expected to worsen the cardiovascular phenotype in MFS.

The extracellular matrix glycoprotein fibrillin-1 in health and disease

“…In order to investigate the impact of FBN1 on kidney, the renal phenotype of mice with under-expressed FBN1 is examined within the context of the MFS model. Mesangial area and glomerular volume are significantly decreased in glomeruli of FBN1-underexpressing mice ( Hartner et al, 2004 ; de Souza et al, 2023 ). FBN1 exists in the mesangial matrix of the glomerulus, and its expression is induced in the acute phase of anti-Thy1.1 glomerulonephritis ( Porst et al, 2006 ).…”