title: The expression of podocyte-specific proteins in parietal epithelial cells is regulated by protein degradation.
abstract: The role of parietal epithelial cells (PECs) in glomerular disease is unclear because they also express podocyte proteins under pathophysiological conditions. To help resolve this, we established a novel PEC isolation technique in rats and mice to investigate which regulatory mechanisms lead to podocyte protein expression in PECs. This pure pool of naive PECs was then compared with PECs in primary culture and immortalized PECs in permanent culture. The naive PECs expressed low levels of podocyte-specific mRNA. Accordingly, in crescentic glomerulonephritis, single PECs activated the podocin promoter in vivo. In primary culture, PECs expressed a distinct morphology from podocytes but with high transcript and protein levels of PEC markers. In contrast to naive PECs, cultured PECs also expressed podocyte proteins, and this correlated with reduced proteolytic activity but not with increased transcript levels. Activation of autophagy or proteasomal degradation decreased the levels of podocyte proteins in PECs, whereas inhibition of proteasomal degradation led to the stabilization of podocyte proteins in PECs. Thus, naive PECs express podocyte transcripts physiologically and these podocyte proteins are stable under pathological conditions through decreased proteolysis.
authors.affiliation: Department of Internal Medicine, Nephrology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sebastian S O
authors.initials: SS
authors.lastname: Guhr
authors.forename: Marlies
authors.initials: M
authors.lastname: Sachs
authors.forename: Anne
authors.initials: A
authors.lastname: Wegner
authors.forename: Jan U
authors.initials: JU
authors.lastname: Becker
authors.forename: Tobias N
authors.initials: TN
authors.lastname: Meyer
authors.forename: Leonie
authors.initials: L
authors.lastname: Kietzmann
authors.forename: Saskia
authors.initials: S
authors.lastname: Schlossarek
authors.forename: Lucie
authors.initials: L
authors.lastname: Carrier
authors.forename: Melanie
authors.initials: M
authors.lastname: Braig
authors.forename: Parmjit S
authors.initials: PS
authors.lastname: Jat
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D002478:Cells, Cultured; D003893:Desmin / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D059748:Proteolysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000378:metabolism*; D059467:Transcriptome / Q000502:physiology
chemical_list: D003893:Desmin; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C113267:nephrin; C001643:podocalyxin