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

TGF-ß1 synthesized by proximal tubular cells (PTC) is an important stimulus of fibrosis in progressive renal disease. TGF-ß1 mRNA has low basal translational efficiency in PTC, and translation is stimulated by profibrotic cytokines.

The aim of this study was to investigate how PTC TGF-ß1 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 Y-box protein 1(YB-1). Recombinant YB-1 was sufficient to form both complexes. RNA competitor experiments confirmed YB-1 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 TGF-ß1 synthesis.

Taken together, our results suggest that in PTC, YB-1 binding to two sites within the TGF-ß1 5’UTR regulates translation, with TGF-ß1 translation requiring YB-1 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 YB-1 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: Show antibodies

TGF-beta1 antibodies: Show antibodies