Parietal epithelial cells maintain the epithelial cell continuum forming Bowman's space in focal segmental glomerulosclerosis

L. Miesen, P. Bándi, B. Willemsen, F. Mooren, T. Strieder, E. Boldrini, V. Drenic, J. Eymael, R. Wetzels, J. Lotz, N. Weiss, E. Steenbergen, T. van Kuppevelt, M. van Erp, J. van der Laak, N. Endlich, M. Moeller, J. Wetzels, J. Jansen and B. Smeets

Disease Models & Mechanisms 2022;15.

DOI PMID Cited by ~3


In the glomerulus, Bowman's space is formed by a continuum of glomerular epithelial cells. In focal segmental glomerulosclerosis (FSGS), glomeruli show segmental scarring, a result of activated parietal epithelial cells (PECs) invading the glomerular tuft. The segmental scars interrupt the epithelial continuum. However, non-sclerotic segments seem to be preserved even in glomeruli with advanced lesions. We studied the histology of the segmental pattern in Munich Wistar Fr\"omter rats, a model for secondary FSGS. Our results showed that matrix layers lined with PECs cover the sclerotic lesions. These PECs formed contacts with podocytes of the uninvolved tuft segments, restoring the epithelial continuum. Formed Bowman's spaces were still connected to the tubular system. In biopsies of patients with secondary FSGS, we also detected matrix layers formed by PECs, separating the uninvolved from the sclerotic glomerular segments. PECs have a major role in the formation of glomerulosclerosis; we show here that in FSGS they also restore the glomerular epithelial cell continuum that surrounds Bowman's space. This process may be beneficial and indispensable for glomerular filtration in the uninvolved segments of sclerotic glomeruli.