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Kidney International: Role of YB-1 in chronic kidney disease

synthesized by proximal tubular cells (PTC) is an important stimulus of fibrosis in progressive renal disease. mRNA has low basal translational efficiency in PTC, and translation is stimulated by profibrotic .


The aim of this study was to investigate how PTC translation is regulated. RNA-EMSA and UV cross-linking detected two protein complexes binding to the TGF-ß1 5’ untranslated region (5’UTR) with molecular weights of 50 and 100 kD. Supershift experiments suggested that both contained . Recombinant YB-1 was sufficient to form both complexes. RNA competitor experiments confirmed binding to two predicted binding sites: nucleotides 67-86 with high affinity, and nucleotides 16-35 with lower affinity. Strong basal YB-1 association with TGF-ß1 mRNA was seen in PTC, this decreased when Platelet Derived Growth Factor was used to activate TGF-ß1 translation. In contrast, knockdown of PTC YB-1 expression abrogated synthesis.

Taken together, our results suggest that in PTC, YB-1 binding to two sites within the TGF-ß1 5’UTR regulates translation, with translation requiring binding to the high affinity (nucleotides 67-86) site, but with YB-1 binding to the low affinity (nucleotides 16-35) site inhibiting translation in the basal state. This demonstrates a mechanism by which synthesis of TGF-ß1 is regulated in PTC, and suggests that may be a desirable therapeutic target in chronic kidney disease.

This YB-1 antibody has been used for the article: YB-1 (N-Term) antibody

Additional YB-1 antibodies:

TGF-beta1 antibodies: