Podocyte adversely impact the health of neighboring parietal epithelial cells in the aged kidney

• Grant number: 22/00073-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): August 15, 2022
• Effective date (End): August 14, 2023
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Karina Thieme
• Grantee: Beatriz Maria Veloso Pereira
• Supervisor: Stuart James Shankland
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: University of Washington, United States
• Associated to the scholarship: 19/10583-0 - Epigenetic regulation of TET and Klotho proteins in Glomerular Disease, BP.DR

Abstract

The overall scope of the problem is that as the US population lives longer, kidney disease becomes more abundant. Elderly patients in particular face worse disease outcomes and they are now the largest group to undergo first-time dialysis. The goal of this proposal is to prove that aged terminally differentiated glomerular epithelial cells, called podocytes, are central to the many glomerular changes with aging. Changes to and loss of podocytes remain the best predictors of age-related glomerulosclerosis and reduced GFR. Major unmet needs are understanding the mechanisms of podocyte aging and the crosstalk between aged podocytes and neighboring parietal epithelial cells (PECs). Our published transcriptome analysis comparing podocytes from aged vs. young mice showed that much to our surprise, transcripts for immune response processes such as the Nlrp3 inflammasome was significantly enriched. Importantly, similar changes were confirmed in human kidney biopsies. Based on these preliminary data, the overall objective is to test a novel paradigm that aged podocytes secrete inflammatory signals that via autocrine and paracrine loops directly impact themselves and PECs respectively. To accomplish this, studies will use newly generated transgenic and mutant mice, and a complimentary co-cell culture approach. These data will ultimately inform improved ways to manage the elderly with kidney disease.