Y-box protein-1 controls transforming growth factor-β1 translation in proximal tubular cells

Fraser, Donald James ORCID: https://orcid.org/0000-0003-0102-9342, Phillips, Aled Owen ORCID: https://orcid.org/0000-0001-9744-7113, Zhang, Xiao Liang, van Roeyen, C. R., Muehlenberg, P., En-Nia, A. and Mertens, P. R. 2008. Y-box protein-1 controls transforming growth factor-β1 translation in proximal tubular cells. Kidney International 73 (6) , pp. 724-732. 10.1038/sj.ki.5002719

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Abstract

Transforming growth factor-1 (TGF-1) mRNA has low basal translational efficiency in proximal tubule cells; however, its translation is stimulated by profibrotic cytokines. We studied the role of the multifunctional Y-box protein-1 (YB-1) in regulating proximal tubule cell TGF-1 translation. Using RNA-electrophoretic mobility shift assays and ultraviolet crosslinking, we found two protein complexes of 50 and 100 kDa, which bound to the TGF-1 mRNA 5'-untranslated region. Supershift studies using antibodies to YB-1 showed that both sites contained YB-1 as did studies with recombinant YB-1, which demonstrated that it was sufficient to form both complexes. RNA competition experiments confirmed YB-1 binding to the two predicted binding sites; one with high affinity and the other with lower affinity. Strong basal YB-1 association with TGF-1 mRNA was found in proximal tubule cells, which decreased when platelet-derived growth factor was used to activate TGF-1 translation. In contrast, knockdown of proximal tubule cell YB-1 expression abrogated TGF-1 synthesis. Our results suggest that TGF-1 translation in proximal tubule cells requires YB-1 binding to a high-affinity site in the 5'-untranslated region of its mRNA; however, binding to a low-affinity site inhibits basal translation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General)
Uncontrolled Keywords:	TGF-β; renal proximal tubule cell; renal fibrosis; diabetic nephropathy
Publisher:	Nature Publishing Group
ISSN:	0085-2538
Last Modified:	05 Nov 2022 16:12
URI:	https://orca.cardiff.ac.uk/id/eprint/25117

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