Abstract
The origin of crescent forming cells in human glomerulonephritis (GN) remains unknown. Some animal studies demonstrated that parietal epithelial cells of Bowman's capsule (PECs) were the main component of proliferating cells and PEC-specific tight junction protein claudin-1 was expressed in crescentic lesions. We investigated the expression of claudin-1 in human GN. Immunohistochemistry for claudin-1 was performed on 17 kidney biopsy samples with crescent formation. Colocalization of claudin-1 with intracellular tight junction protein ZO-1 was also evaluated by immunofluorescence double staining. Claudin-1 is expressed mainly at the cell to cell contact site of proliferating cells in cellular crescentic lesions in patients with these forms of human GN. Small numbers of crescent forming cells showed extrajunctional localization of claudin-1. Colocalization of claudin-1 with ZO-1 was found at cell to cell contact sites of adjacent proliferating cells. In control samples, staining of claudin-1 was positive in PECs, but not in podocytes. Our findings suggest that claudin-1 contributes to crescent formation as a component of the tight junction protein complex that includes ZO-1. Co-localization of claudin-1 with ZO-1 implies the formation of functional tight junction complexes in crescentic lesions to prevent the interstitial damage caused by penetration of filtered molecules from Bowman's space.
Highlights
Extracapillary proliferative cellular lesions or cellular crescents are a hallmark of severe inflammatory reactions in glomeruli and have been documented in various forms of glomerulonephritis (GN) [1]
We investigated the expression of claudin-1 and its colocalization with ZO-1 in various human glomerular diseases including IgA nephropathy, purpura nephritis, anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (MPO-ANCA and PR-3 ANCA), anti-glomerular basement membrane (GBM)-RPGN, and lupus nephritis
Nonjunctional mislocalization of claudin-1 was occasionally recognized in crescent forming cells, but not in parietal epithelial cells of Bowman’s capsule (PECs) of control renal samples
Summary
Extracapillary proliferative cellular lesions or cellular crescents are a hallmark of severe inflammatory reactions in glomeruli and have been documented in various forms of glomerulonephritis (GN) [1]. Though the origin of these crescentic lesions remains controversial, recent studies have clarified that inflammatory cells, and intrinsic glomerular epithelial cells (i.e., parietal epithelial cells of Bowman’s capsule (PECs) and glomerular epithelial cells or podocytes) contribute to the development of these crescents [2]. Smeets et al demonstrated, using the genetic cell lineage tracing method, that PECs constitute the principal component of cellular crescents, especially at the early stage, in animal models of crescentic GN [3]. Claudin is a tetraspan-transmembrane protein and is a crucial component of tight junction complexes in epithelial and endothelial cells [4, 5]. Claudin-1 is expressed in the tight junctions of PECs in both murine models and human patients with GN and is regarded as a marker of PECs [3, 6, 7]
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