Human parietal epithelial cells (PECs) and proteinuria in lupus nephritis: a role for ClC-5, megalin, and cubilin?

Monica Ceol; Lisa Gianesello; Hernan Trimarchi; Alberto Migliorini; Giovanna Priante; Claudia M Radu; Elena Naso; Annalisa Angelini; Lorenzo A Calò; Franca Anglani; Dorella Del Prete

doi:10.1007/s40620-023-01725-6

Human parietal epithelial cells (PECs) and proteinuria in lupus nephritis: a role for ClC-5, megalin, and cubilin?

J Nephrol. 2023 Dec;36(9):2499-2506. doi: 10.1007/s40620-023-01725-6. Epub 2023 Aug 18.

Authors

Affiliations

¹ Nephrology Unit- Kidney Histomorphology and Molecular Biology Laboratory, Department of Medicine-DIMED, University of Padua, Via Giustiniani, 2, 235128, Padua, Italy.
² Nephrology Service, Hospital Británico de Buenos Aires, Buenos Aires, Argentina.
³ General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, University of Padua, Padua, Italy.
⁴ Cardiovascular Pathology and Pathological Anatomy, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy.
⁵ Nephrology Unit- Kidney Histomorphology and Molecular Biology Laboratory, Department of Medicine-DIMED, University of Padua, Via Giustiniani, 2, 235128, Padua, Italy. dorella.delprete@unipd.it.

^# Contributed equally.

Abstract

Background: Parietal epithelial cells are a heterogeneous population of cells located on Bowman's capsule. These cells are known to internalize albumin with a still undetermined mechanism, although albumin has been shown to induce phenotypic changes in parietal epithelial cells. Proximal tubular cells are the main actors in albumin handling via the macromolecular complex composed by ClC-5, megalin, and cubilin. This study investigated the role of ClC-5, megalin, and cubilin in the parietal epithelial cells of kidney biopsies from proteinuric lupus nephritis patients and control subjects and identified phenotypical changes occurring in the pathological milieu.

Methods: Immunohistochemistry and immunofluorescence analyses for ClC-5, megalin, cubilin, ANXA3, podocalyxin, CD24, CD44, HSA, and LTA marker were performed on 23 kidney biopsies from patients with Lupus Nephritis and 9 control biopsies (obtained from nephrectomies for renal cancer).

Results: Two sub-populations of hypertrophic parietal epithelial cells ANXA3⁺/Podocalyxin^-/CD44^-, both expressing ClC-5, megalin, and cubilin and located at the tubular pole, were identified and characterized: the first one, CD24⁺/HSA^-/LTA^- had characteristics of human adult parietal epithelial multipotent progenitors, the second one, CD24^-/LTA⁺/HSA⁺ committed to become phenotypically proximal tubular cells. The number of glomeruli presenting hypertrophic parietal epithelial cells positive for ClC-5, megalin, and cubilin were significantly higher in lupus nephritis patients than in controls.

Conclusions: Our results may provide further insight into the role of hypertrophic parietal epithelial cells located at the tubular pole and their possible involvement in protein endocytosis in lupus nephritis patients. These data also suggest that the presence of hypertrophic parietal epithelial cells in Bowman's capsule represents a potential resource for responding to protein overload observed in other glomerulonephritis.

Keywords: ClC-5; Cubilin; Hypertrophic PECs; Kidney biopsy; Megalin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Albumins / metabolism
Epithelial Cells / metabolism
Humans
Kidney Tubules, Proximal
Low Density Lipoprotein Receptor-Related Protein-2* / metabolism
Lupus Nephritis*
Proteinuria / etiology

Substances

intrinsic factor-cobalamin receptor
Low Density Lipoprotein Receptor-Related Protein-2
Albumins

Grants and funding

CPDA157159/University of Padua