Heterogeneous nuclear ribonucleoprotein K modulates angiotensinogen gene expression in kidney cells

Chih Chang Wei, Shao Ling Zhang, Yun-Wen Chen, Deng Fu Guo, Julie R. Ingelfinger, Karol Bomsztyk, John S.D. Chan

Research output: Contribution to journalArticle

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Abstract

The present studies aimed to identify the 70-kDa nuclear protein that binds to an insulin-responsive element in the rat angiotensinogen gene promoter and to define its action on angiotensinogen gene expression. Nuclear proteins were isolated from rat kidney proximal tubular cells and subjected to two-dimensional electrophoresis. The 70-kDa nuclear protein was detected by Southwestern blotting and subsequently identified by mass spectrometry, which revealed that it was identical to 65-kDa heterogeneous nuclear ribonucleoprotein K (hnRNP K). hnRNP K bound to the insulin-responsive element of the rat angiotensinogen gene was revealed by a gel mobility shift assay and chromatin immunoprecipitation assay. hnRNP K inhibited angiotensinogen mRNA expression and promoter activity. In contrast, hnRNP K down-expression by small interference RNA enhanced angiotensinogen mRNA expression. Moreover, hnRNP K interacted with hnRNP F in pulldown and co-immunoprecipitation assays. Co-transfection of hnRNPK and hnRNP F further suppressed angiotensinogen mRNA expression. Finally, in vitro and in vivo studies demonstrated that high glucose increases and insulin inhibits hnRNP K expression in rat kidney proximal tubular cells. In conclusion, our experiments revealed that hnRNP K is a nuclear protein that binds to the insulin-responsive element of the rat angiotensinogen gene promoter and modulates angiotensinogen gene transcription in the kidney.

Original languageEnglish
Pages (from-to)25344-25355
Number of pages12
JournalJournal of Biological Chemistry
Volume281
Issue number35
DOIs
Publication statusPublished - 2006 Sep 1

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Heterogeneous-Nuclear Ribonucleoprotein K
Angiotensinogen
Gene expression
Kidney
Gene Expression
Rats
Nuclear Proteins
Heterogeneous-Nuclear Ribonucleoprotein Group F-H
Genes
Insulin
Assays
Messenger RNA
Southwestern Blotting
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Transcription
RNA Interference
Electrophoresis
Immunoprecipitation
Chromatin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wei, C. C., Zhang, S. L., Chen, Y-W., Guo, D. F., Ingelfinger, J. R., Bomsztyk, K., & Chan, J. S. D. (2006). Heterogeneous nuclear ribonucleoprotein K modulates angiotensinogen gene expression in kidney cells. Journal of Biological Chemistry, 281(35), 25344-25355. https://doi.org/10.1074/jbc.M601945200
Wei, Chih Chang ; Zhang, Shao Ling ; Chen, Yun-Wen ; Guo, Deng Fu ; Ingelfinger, Julie R. ; Bomsztyk, Karol ; Chan, John S.D. / Heterogeneous nuclear ribonucleoprotein K modulates angiotensinogen gene expression in kidney cells. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 35. pp. 25344-25355.
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Heterogeneous nuclear ribonucleoprotein K modulates angiotensinogen gene expression in kidney cells. / Wei, Chih Chang; Zhang, Shao Ling; Chen, Yun-Wen; Guo, Deng Fu; Ingelfinger, Julie R.; Bomsztyk, Karol; Chan, John S.D.

In: Journal of Biological Chemistry, Vol. 281, No. 35, 01.09.2006, p. 25344-25355.

Research output: Contribution to journalArticle

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