Heterogeneous Nuclear Ribonucleoprotein F Suppresses Angiotensinogen Gene Expression and Attenuates Hypertension and Kidney Injury in Diabetic Mice

Corresponding author: John S.D. Chan, .
Diabetes (Impact Factor: 8.1). 06/2012; 61(10):2597-608. DOI: 10.2337/db11-1349
Source: PubMed


We investigated the impact of heterogeneous nuclear ribonucleoprotein F (hnRNP F) overexpression on angiotensinogen (Agt) gene expression, hypertension, and renal proximal tubular cell (RPTC) injury in high-glucose milieu both in vivo and in vitro. Diabetic Akita transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs were created, and the effects on systemic hypertension, Agt gene expression, renal hypertrophy, and interstitial fibrosis were studied. We also examined immortalized rat RPTCs stably transfected with control plasmid or plasmid containing hnRNP F cDNA in vitro. The results showed that hnRNP F overexpression attenuated systemic hypertension, suppressed Agt and transforming growth factor-β1 (TGF-β1) gene expression, and reduced urinary Agt and angiotensin II levels, renal hypertrophy, and glomerulotubular fibrosis in Akita hnRNP F-Tg mice. In vitro, hnRNP F overexpression prevented the high-glucose stimulation of Agt and TGF-β1 mRNA expression and cellular hypertrophy in RPTCs. These data suggest that hnRNP F plays a modulatory role and can ameliorate hypertension, renal hypertrophy, and interstitial fibrosis in diabetes. The underlying mechanism is mediated, at least in part, via the suppression of intrarenal Agt gene expression in vivo. hnRNP F may be a potential target in the treatment of hypertension and kidney injury in diabetes.

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Available from: Chao-Sheng Lo, Sep 03, 2014
    • "Remarkably, a growing body of evidence is indicating that mis-regulation of hnRNPs may underlie a variety of human diseases. Indeed, mis-regulation of hnRNP levels and of the post-transcriptional modifications catalysed by hnRNPs have been reported in cancer (Carpenter et al. 2006; Gao et al. 2013; Dery et al. 2011; Patry et al. 2003), diabetes, hypertension (Lo et al. 2012 ) and also in neurodegenerative diseases (Hanson et al. 2012; Lee et al. 2012). Here, we provide a comprehensive overview of the hnRNPs composition, nuclear localization, organization and function in the model system D. melanogaster, emphasizing the use of fruit fly as an elective system for studying hnRNPs' biology as well as diseases connected with their mis-function. "
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    ABSTRACT: Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a highly conserved family of RNA-binding proteins able to associate with nascent RNAs in order to support their localization, maturation and translation. Research over this last decade has remarked the importance of gene regulatory processes at post-transcriptional level, highlighting the emerging roles of hnRNPs in several essential biological events. Indeed, hnRNPs are key factors in regulating gene expression, thus, having a number of roles in many biological pathways. Moreover, failure of the activities catalysed by hnRNPs affects various biological processes and may underlie several human diseases including cancer, diabetes and neurodegenerative syndromes. In this review, we summarize some of hnRNPs' roles in the model organism Drosophila melanogaster, particularly focusing on their participation in all aspects of post-transcriptional regulation as well as their conserved role and involvement in the aetiology of human pathologies.
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