CWRU Links

Crosstalk between visceral and parietal cells of the glomerular epithelium in proteinuric diseases

Chronic kidney diseases (CKD) are a major public health problem. Forty million Americans live with kidney diseases, and nearly 700,000 have evolved to end-stage kidney disease (ESKD). Importantly, advanced CKD constitutes a racial and ethnic disparity as different glomerulopathies, including Focal Segmental Glomerulosclerosis (FSGS) and hypertension-attributed-ESKD (H-ESKD) are much higher in minorities. The kidney glomerulus is a tuft of small blood vessels located at the beginning of the nephron that controls the filtration of blood into Bowman’s space to form urine. At the visceral side of Bowman’s space, surrounding the tuft, are the podocytes, which play a critical role in maintaining the filtration barrier. The parietal side of Bowman’s space is lined by parietal epithelial cells (PECs). Several podocytopathies are characterized by podocyte dedifferentiation, diffuse foot processes and loss of the slit diaphragm resulting in heavy proteinuria. Even though podocyte effacement is a hallmark of proteinuric diseases, the interaction between this cell type and PECs during proteinuria and remission remains obscure. Injection anti-nephrin antibodies to rodents causes a redistribution of slit-diaphragm proteins similar to that observed in kidney biopsies of patients with nephrotic syndrome, which results in proteinuria and lesions compatible with FSGS. We will use this model to conduct histological and transcriptional studies at single cell resolution to determine whether the restoration of the epithelial cell continuum during proteinuria and remission involves the replacement of podocytes by PECs