The expression of podocyte-specific proteins in parietal epithelial cells is regulated by protein degradation
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The expression of podocyte-specific proteins in parietal epithelial cells is regulated by protein degradation. / Guhr, Sebastian SO; Sachs, Marlies; Wegner, Anne; Becker, Jan U; Meyer, Tobias N; Kietzmann, Leonie; Schlossarek, Saskia; Carrier, Lucie; Balabanov, Melanie; Jat, Parmjit S; Stahl, Rolf A K; Meyer-Schwesinger, Catherine.
in: KIDNEY INT, Jahrgang 84, Nr. 3, 01.09.2013, S. 532-44.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The expression of podocyte-specific proteins in parietal epithelial cells is regulated by protein degradation
AU - Guhr, Sebastian SO
AU - Sachs, Marlies
AU - Wegner, Anne
AU - Becker, Jan U
AU - Meyer, Tobias N
AU - Kietzmann, Leonie
AU - Schlossarek, Saskia
AU - Carrier, Lucie
AU - Balabanov, Melanie
AU - Jat, Parmjit S
AU - Stahl, Rolf A K
AU - Meyer-Schwesinger, Catherine
PY - 2013/9/1
Y1 - 2013/9/1
N2 - 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.
AB - 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.
U2 - 10.1038/ki.2013.115
DO - 10.1038/ki.2013.115
M3 - SCORING: Journal article
C2 - 23615505
VL - 84
SP - 532
EP - 544
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 3
ER -
