CD44 Expression in Renal Tissue Is Associated with an Increase in Urinary Levels of Complement Components in Chronic Glomerulopathies

• Published in: International journal of molecular sciences 2023-04, Vol.24 (8), p.7190
• Main Authors: Chebotareva, Natalia, Vinogradov, Anatoliy, Tsoy, Larisa, Varshavskiy, Vladimir, Stoljarevich, Ekaterina, Bugrova, Anna, Lerner, Yulia, Krasnova, Tatyana, Biryukova, Evgeniya, Kononikhin, Alexey S
• Format: Article
• Language: English
• Subjects: CD44; Chronic Disease; Communication; complement; Fibrosis; Glomerulonephritis - complications; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental - metabolism; Hematuria; Humans; Hyaluronan Receptors - metabolism; Immunoglobulin A; Kidney diseases; Medical research; Medicine, Experimental; parietal epithelial cells; Proteinuria; renal fibrogenesis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24087190

It is suggested that activated CD44+ cells play a profibrogenic role in the pathogenesis of active glomerulopathies. Complement activation is also involved in renal fibrogenesis. The aim of the study was to evaluate the role of the activation of CD44+ cells in the kidney tissue and complement components' filtration to the urine as factors of renal tissue fibrosis in patients with glomerulopathies. In total, 60 patients with active glomerulopathies were included in our study: 29 patients with focal segmental glomerulosclerosis (FSGS), 10 patients with minimal change disease (MCD), 10 patients with membranous nephropathy (MN), and 11 patients with IgA nephropathy. The immunohistochemical peroxidase method was used to study the expression of CD44+ in kidney biopsies. Components of complement were analyzed in urine by the multiple reaction monitoring (MRM) approach using liquid chromatography. Strong CD44 expression was noted predominantly in PEC and mesangial cells (MC) in patients with FSGS, and to a lesser extent, in patients with MN and IgA nephropathy, and it was absent in patients with MCD. Expression of profibrogenic CD44+ in glomeruli correlated with the levels of proteinuria and complement C2, C3, and C9 components, and CFB and CFI in urine. The CD44+ expression scores in the renal interstitium correlated with the level of C3 and C9 components of complement in the urine and the area of tubulo-interstitial fibrosis. The strongest expression of CD44+ was found in the glomeruli (MC, PEC, and podocytes) of patients with FSGS compared with other glomerulopathies. The CD44 expression score in the glomeruli and interstitium is associated with high levels of complement components in the urine and renal fibrosis.