INTEGRINS AND CD2AP EXPRESSION AFTER ALBUMIN OVERLOAD IN PODOCYTE CELL CULTURE WITH AND WITHOUT INJURY

• Grant number: 24/13911-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2024
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mara Sanches Guaragna
• Grantee: Heber da Silva Antonio
• Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/10387-6 - In vitro evaluation of molecular consequences of albumin overload in podocytes, AP.R
• Associated scholarship(s): 25/10344-6 - CD2AP and alfa3 beta1 and alfav beta3 integrins Expression and Localization Assays after Albumin Overload in 3D Co-culture Spheroid Model GlomSpheres with and without Damage, BE.EP.MS

Abstract

Proteinuria is an important sign and prognostic marker for the progression of chronic kidney disease (CKD). Proteinuria typically indicates a compromised selectivity of the glomerular filtration barrier (GFB), which consists of three layers: the fenestrated endothelium, the glomerular basement membrane, and the podocytes. Podocytes are highly specialized cells whose foot processes interdigitate to form slit diaphragms (SD). Foot processes are divided into three primary regions: the slit diaphragm (SD) domain, the apical membrane domain (AMD), and the basal membrane domain (BMD). Several molecules contribute to the maintenance of the GFB, including the adapter protein CD2AP in the SD domain and integrins ±3²1 and ±V²3 in the BMD domain. While podocyte injury is known to cause progressive albuminuria, the extent to which proteinuria exacerbates this injury remains a subject of debate. Few studies have explored the molecular consequences of prolonged albumin overload in human podocytes in vitro. This study aims to determine whether there are differences in the protein expression of the genes CD2AP, ITGA3, ITGB1, ITGAV, and ITGB3 in human podocytes without and with previous damage induced with the aminoglycoside puromycin (PAN), under the following conditions: a) progressive albumin overload, and b) albumin removal in conditions where expression changes occur. This study should identify molecular pathways that can be further investigated in animal models and potentially serve as therapeutic targets, contributing to slowing the progression of CKD in many patients.