title: Recruitment of podocytes from glomerular parietal epithelial cells.
abstract: Loss of a critical number of podocytes from the glomerular tuft leads to glomerulosclerosis. Even in health, some podocytes are lost into the urine. Because podocytes themselves cannot regenerate, we postulated that glomerular parietal epithelial cells (PECs), which proliferate throughout life and adjoin podocytes, may migrate to the glomerular tuft and differentiate into podocytes. Here, we describe transitional cells at the glomerular vascular stalk that exhibit features of both PECs and podocytes. Metabolic labeling in juvenile rats suggested that PECs migrate to become podocytes. To prove this, we generated triple-transgenic mice that allowed specific and irreversible labeling of PECs upon administration of doxycycline. PECs were followed in juvenile mice beginning from either postnatal day 5 or after nephrogenesis had ceased at postnatal day 10. In both cases, the number of genetically labeled cells increased over time. All genetically labeled cells coexpressed podocyte marker proteins. In conclusion, we demonstrate for the first time recruitment of podocytes from PECs in juvenile mice. Unraveling the mechanisms of PEC recruitment onto the glomerular tuft may lead to novel therapeutic approaches to renal injury.
authors.affiliation: Division of Nephrology and Immunology, Rheinisch Westfälische Technische Hochschule University of Aachen, Aachen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Appel
authors.forename: David B
authors.initials: DB
authors.lastname: Kershaw
authors.forename: Bart
authors.initials: B
authors.lastname: Smeets
authors.forename: Gang
authors.initials: G
authors.lastname: Yuan
authors.forename: Astrid
authors.initials: A
authors.lastname: Fuss
authors.forename: Björn
authors.initials: B
authors.lastname: Frye
authors.forename: Marlies
authors.initials: M
authors.lastname: Elger
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Kriz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Moeller
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009399:Nephrons / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism