Y-box protein 1 mediates PDGF-B effects in mesangioproliferative glomerular disease.
The pivotal role of PDGF-B for mesangioproliferative glomerular disease is well established. Here, Y-box protein-1 (YB-1) was identified as a downstream signaling target of PDGF-B. In healthy kidney cells, YB-1 was located predominantly within the nuclear compartment. Subsequent to PDGF-B infusion and in the course of anti-Thy1.1-induced mesangioproliferative glomerulonephritis, relocalization of YB-1 into the cytoplasm was observed. In experimental models that lack profound mesangial cell proliferation (e.g., Puromycin-nephrosis, passive Heyman nephritis, spontaneous normotensive nephrosclerosis, hyperlipidemic diabetic nephropathy), YB-1 remained nuclear. This translocation coincided with upregulation of YB-1 protein levels within the mesangial compartment. Increased YB-1 expression and subcellular shuttling was dependent on PDGF-B signaling via the mitogen-activated protein kinase pathway because these alterations were prevented by specific PDGF aptamers and the mitogen-activated protein kinase pathway inhibitor U0126. Furthermore, PDGF-B strongly induced YB-1 expression in vitro. This induction was important because RNAi-dependent knockdown of YB-1 abolished the mitogenic PDGF-B effect. Taken together, YB-1 seems to represent a specific and necessary PDGF-B target in mesangioproliferative glomerular disease.
van Roeyen
Claudia R C
CR
Medical Clinic II, University Hospital Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.
Eitner
Frank
F
Martinkus
Sandra
S
Thieltges
Sabrina R
SR
Ostendorf
Tammo
T
Bokemeyer
Dirk
D
Lüscher
Bernhard
B
Lüscher-Firzlaff
Juliane M
JM
Floege
Juergen
J
Mertens
Peter R
PR
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D005920:Glomerular Mesangium; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology*; D006801:Humans; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000378:metabolism; D021381:Protein Transport; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D051840:Y-Box-Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D051840:Y-Box-Binding Protein 1