Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.
Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase-PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations: CD133(+)CD24(+)podocalyxin (PDX)(-)nestin(-) renal progenitors, CD133(+)CD24(+)PDX(+)nestin(+) transitional cells, and CD133(-)CD24(-)PDX(+)nestin(+) differentiated podocytes. In addition, TGF-beta induced CD133(+)CD24(+) progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.
Smeets
Bart
B
Department of Pathology, Radboud University Nijmegen Medical Center, Geert Grooteplein 24, Nijmegen, Netherlands. b.smeets@pathol.umcn.nl
Angelotti
Maria Lucia
ML
Rizzo
Paola
P
Dijkman
Henry
H
Lazzeri
Elena
E
Mooren
Fieke
F
Ballerini
Lara
L
Parente
Eliana
E
Sagrinati
Costanza
C
Mazzinghi
Benedetta
B
Ronconi
Elisa
E
Becherucci
Francesca
F
Benigni
Ariela
A
Steenbergen
Eric
E
Lasagni
Laura
L
Remuzzi
Giuseppe
G
Wetzels
Jack
J
Romagnani
Paola
P
D000071916:AC133 Antigen; D053687:Adult Stem Cells / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D015703:Antigens, CD / Q000378:metabolism; D050476:Bowman Capsule / Q000378:metabolism / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000473:pathology; D005921:Glomerulonephritis / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D050199:Podocytes / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D012795:Sialoglycoproteins / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; C000606023:PROM1 protein, human; D010455:Peptides; D012795:Sialoglycoproteins; C001643:podocalyxin