NF-κB mediated miR-26a regulation in cardiac fibrosis

Chuanyu Wei, Il Kwon Kim, Sandeep Kumar, Samantha Jayasinghe, Nayeon Hong, Giovanna Castoldi, Daniele Catalucci, W. Keith Jones, Sudhiranjan Gupta

Research output: Contribution to journalArticle

Abstract

Micro-RNAs (miRNAs) are a class of small non-coding RNAs, recently emerged as a post-transcriptional regulator having a key role in various cardiac pathologies. Among them, cardiac fibrosis that occurs as a result from an imbalance of extracellular matrix proteins turnover and is a highly debilitating process that eventually lead to organ dysfunction. An emerging theme on is that miRNAs participate in feedback loop with transcription factors that regulate their transcription. NF-κB, a key transcription factor regulator controls a series of gene program in various cardiac diseases through positive and negative feedback mechanism. But, NF-κB mediated miRNA regulation in cardiac fibrosis remains obscure. Bioinformatics analysis revealed that miR-26a has targets collagen I and CTGF and possesses putative NF-κB binding element in its promoter region. Here, we show that inhibition of NF-κB in cardiac fibroblast restores miR-26a expression, attenuating collagen I, and CTGF gene expression in the presence of Ang II, conferring a feedback regulatory mechanism in cardiac fibrosis. The target genes for miR-26a were confirmed using 3′-UTR luciferase reporter assays for collagen I and CTGF genes. Using NF-κB reporter assays, we determine that miR-26a overexpression inhibits NF-κB activity. Finally, we show that miR-26a expression is restored along with the attenuation of collagen I and CTGF genes in cardiac specific IkBa triple mutant transgenic mice (preventing NF-κB activation) subjected to 4 weeks transverse aortic banding (TAC), compared to wild type (WT) mice. The data indicate a potential role of miR-26a in cardiac fibrosis and, offer novel therapeutic intervention.

Original languageEnglish
Pages (from-to)1433-1442
Number of pages10
JournalJournal of Cellular Physiology
Volume228
Issue number7
DOIs
Publication statusPublished - Jul 2013

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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  • Cite this

    Wei, C., Kim, I. K., Kumar, S., Jayasinghe, S., Hong, N., Castoldi, G., Catalucci, D., Jones, W. K., & Gupta, S. (2013). NF-κB mediated miR-26a regulation in cardiac fibrosis. Journal of Cellular Physiology, 228(7), 1433-1442. https://doi.org/10.1002/jcp.24296