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TY - THES AU - Zhu, Cheng TI - Expression and regulation of cold shock proteins in inflammatory kidney and liver diseases CY - Aachen PB - Publikationsserver der RWTH Aachen University M1 - RWTH-CONV-143088 SP - 106 S. : Ill., graph. Darst. PY - 2012 N1 - Aachen, Techn. Hochsch., Diss., 2012 AB - Cold shock proteins have attracted considerable attention in the context of carcinogenesis given their potent roles. The participation of cold shock protein DbpB/YB-1 in the course of inflammatory diseases has only recently been described and visualized in experimental models of mesangioproliferative glomerular disease and liver fibrotic diseases. The fundamental question addressed here is whether another prominent member of the cold shock protein family, DbpA, is also regulated in mesangioproliferative disease, although it has been primarily described as protein with activities in epithelial tubular cell proliferation and differentiation. Whereas in healthy kidney tissue DbpA protein was predominantly detected in vascular smooth muscle cells a profound up-regulation of DbpA protein expression within the mesangial compartment was evidenced in human kidney biopsies diagnosed with mesangioproliferative IgA or lupus nephritis. Such a mesangial up-regulation was recapitulated in an experimental model, the anti-Thy1.1 nephritis. Given the pivotal role of PDGF-B signaling in this disease two interventions were performed, that is the application of PDGF-B neutralizing aptamers and MAPK/Erk signaling inhibitor U0126. Both interventions resulted in markedly decreased DbpA expression. Conversely, continuous PDGF-B infusion induced DbpA expression predominantly within the mesangial compartment in rats. In vitro studies of human and rat mesangial cells confirmed the PDGF-B stimulatory effect at transcript and protein levels. Notably, DbpA protein isoforms exhibit sizes of 44, 50 and 55 kDa, with predominance of the 44 kDa isoform. Conditioned cell culture medium of mesangial cells also revealed that PDGF-B induced secretion of DbpA (p50) in a time- and concentration-dependent manner occurs. Taken together, cold shock protein DbpA represents a novel target of PDGF-B signaling in mesangioproliferative glomerular disease. In inflammatory liver diseases we observed both DbpA and DbpB/YB-1 up-regulation, however with different expression patterns. Whereas DbpA over-expressing cells were identified as activated macrophages and hepatic stellate cells, DbpB/YB-1 immunopositive cells were mainly hepatic epithelial cells. This may indicate differential roles that CSP fulfill in inflammatory liver diseases: DbpA may be functional in the early phases of fibrogenesis while DbpB/YB-1 may be involved in liver regeneration and re-modeling. KW - Proliferative kidney disease (SWD) KW - Entzündung (SWD) KW - Kälteschock-Proteine (SWD) KW - Nierenkrankheit (SWD) KW - Leberkrankheit (SWD) LB - PUB:(DE-HGF)11 UR - https://publications.rwth-aachen.de/record/82710 ER -