Type

Journal Article

Authors

Catherine Godson
Finian Martin
Alexander P Maxwell
David A Savage
Patrick J Guiry
Syed Tasadaque Ali-Shah
Denise M Sadlier
Madeline Murphy
Debra F Higgins
Neil G Docherty
and 5 others

Subjects

Pharmacology

Topics
kidney signal transduction kidney tubules proximal pathology cells cultured lipoxin a4 receptor notch1 notch1 protein human lipoxins transforming growth factor beta1 metabolism humans thrombospondins pharmacology fibronectins drug effects micrornas cadherins mirnlet7 microrna human fibrosis

Lipoxins attenuate renal fibrosis by inducing let-7c and suppressing TGFβR1. (2013)

Abstract Lipoxins, which are endogenously produced lipid mediators, promote the resolution of inflammation, and may inhibit fibrosis, suggesting a possible role in modulating renal disease. Here, lipoxin A4 (LXA4) attenuated TGF-β1-induced expression of fibronectin, N-cadherin, thrombospondin, and the notch ligand jagged-1 in cultured human proximal tubular epithelial (HK-2) cells through a mechanism involving upregulation of the microRNA let-7c. Conversely, TGF-β1 suppressed expression of let-7c. In cells pretreated with LXA4, upregulation of let-7c persisted despite subsequent stimulation with TGF-β1. In the unilateral ureteral obstruction model of renal fibrosis, let-7c upregulation was induced by administering an LXA4 analog. Bioinformatic analysis suggested that targets of let-7c include several members of the TGF-β1 signaling pathway, including the TGF-β receptor type 1. Consistent with this, LXA4-induced upregulation of let-7c inhibited both the expression of TGF-β receptor type 1 and the response to TGF-β1. Overexpression of let-7c mimicked the antifibrotic effects of LXA4 in renal epithelia; conversely, anti-miR directed against let-7c attenuated the effects of LXA4. Finally, we observed that several let-7c target genes were upregulated in fibrotic human renal biopsies compared with controls. In conclusion, these results suggest that LXA4-mediated upregulation of let-7c suppresses TGF-β1-induced fibrosis and that expression of let-7c targets is dysregulated in human renal fibrosis.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Catherine Godson, Finian Martin, Alexander P Maxwell, David A Savage, Patrick J Guiry, Syed Tasadaque Ali-Shah, Denise M Sadlier, Madeline Murphy, Debra F Higgins, Neil G Docherty and 5 others

Experts in our system

1
Catherine Godson
University College Dublin
Total Publications: 93
 
2
Finian Martin
University College Dublin
Total Publications: 81
 
3
Patrick J Guiry
University College Dublin
Total Publications: 47
 
4
Syed Tasadaque Ali-Shah
University College Dublin
 
5
Madeline Murphy
University College Dublin
Total Publications: 37
 
6
Debra F Higgins
University College Dublin
Total Publications: 11
 
7
Neil G Docherty
University College Dublin
Total Publications: 57