New treatment options for glomerulosclerosis
Currently, there are limited options for treatment of glomerulosclerosis available. In previous studies in experimental models of glomerulosclerosis, we have shown that activated parietal epithelial cells (PECs) are crucially involved in the development of glomerulosclerosis. These results were validated in human biopsies. From these studies we proposed that persistent activation of PECs is driving disease progression and that pharmacological inactivation of PECs represents an effective and targeted treatment option to slow loss of renal function.
Our current studies are aimed to unravel the molecular mechanism driving PEC activation and subsequent glomerulosclerosis. The knowledge that will be acquired from these studies is necessary for the identification of new diagnostic and prognostic markers and of specific therapeutic targets.
To understand proximal tubular cell regeneration
Tubular cell injury is a common finding in biopsies of patients with acute kidney injury (AKI), as well as in chronic kidney disease (CKD). Tubular cell injury occurs in response to a variety of renal insults, most commonly ischemia. Nevertheless, tubules have a remarkable capacity to regenerate lost cells. Surviving proximal tubular cells are the major source for new proximal tubular cells. These surviving tubular cells acquire a different phenotype, the so called scattered tubular cell (STC) phenotype, which is transient and dependent of a specific transcriptional program facilitating tubular cell survival and regeneration.
We aim to identify the yet unknown molecular processes underlying this phenotypic switch, which is a prerequisite for developing specific therapies for prevention and recovery of AKI/CKD.
– VIDI grant ZonMw
– VENI grant ZonMw
– Radboudumc Hypatia grant
– Dutch Kindey Foundation
Dr. Jitske Jansen, member of the nephropathology research group, has received a Veni grant of 250,000 Euro from the Netherlands Organization for Scientific Research (NWO). Project title: The REPAIR study: Regeneration of kidnEy ePitheliAl cells crossIng boRders
Our recent publication in Pediatric Nephrology. February 2019 Nephrotic syndrome in a dish: recent developments in modeling in vitro. In this review, we highlight the molecular basis of nephrotic syndrome and discuss requirements to accurately study nephrotic syndrome in vitro, including an overview of specific podocyte markers, cutting-edge stem cell organoids, and the implementation of microfluidic platforms. The development of (patho) physiologically relevant glomerular models will accelerate the identification of molecular targets involved in nephrotic syndrome and
An interview with researcher Jennifer Eymael about her research into scarring in kidney diseases. This study was published in December 2017 in Kidney International. Interview for NierNieuws (Kidney News) “Niercellen maken littekenvorming zelf erger” (article in Dutch)
Kidney Int. March 2018, p626–642 CD44 is required for the pathogenesis of experimental crescentic glomerulonephritis and collapsing focal segmental glomerulosclerosis. J. Eymael et al. A key feature of glomerular diseases such as crescentic glomerulonephritis and focal segmental glomerulosclerosis is the activation, migration and proliferation of parietal epithelial cells. CD44-positive activated parietal epithelial cells have been identified in proliferative cellular lesions in glomerular disease. However, it remains unknown whether CD44-positive parietal epithelial cells contribute to the pathogenesis of