Type

Journal Article

Authors

Catherine Godson
Cormac T. Taylor
Aidan Ryan
Cliodhna Cullen
Carsten C. Scholz
Eoin P Brennan
Karen A Nolan

Subjects

Biochemistry

Topics
thrombospondin 1 calcium binding proteins membrane proteins pharmacology phosphorylation cadherins nephritis interstitial fibrosis protein stability antagonists inhibitors epithelial cells kidney cell hypoxia actins hypoxia inducible factor 1 alpha subunit ergocalciferols 1 25 dihydroxyergocalciferol hif1a protein human endothelial pas domain containing protein 1 intercellular signaling peptides and proteins transforming growth factor beta1 cell line transformed humans drug effects smad2 protein acta2 protein human basic helix loop helix transcription factors pathology metabolism paricalcitol biosynthesis serrate proteins rna interference phosphatidylinositol 3 kinases

Paricalcitol protects against TGF-β1-induced fibrotic responses in hypoxia and stabilises HIF-α in renal epithelia. (2014)

Abstract Epithelial injury and tubulointerstitial fibrosis (TIF) within a hypoxic microenvironment are associated with progressive loss of renal function in chronic kidney disease [CKD]. Transforming growth factor beta-1 (TGF-β1) is an important mediator of renal fibrosis. Growing evidence suggests that Vitamin D [1,25-(OH)2D] and its analogues may have a renoprotective effect in CKD. Here we examined the protective effect of the vitamin D analogue paricalcitol [PC; 19-nor-1α,3β,25-trihydroxy-9,10-secoergosta-5(Z),7(E) 22(E)-triene] on the responses of human renal epithelial cells to TGF-β1. PC attenuated TGF-β1-induced Smad 2 phosphorylation and upregulation of the Notch ligand Jagged-1, α-smooth muscle actin and thrombospondin-1 and prevented the TGF-β1-mediated loss of E-Cadherin. To mimic the hypoxic milieu of CKD we cultured renal epithelial cells in hypoxia [1% O2] and observed similar attenuation by PC of TGF-β1-induced fibrotic responses. Furthermore, in cells cultured in normoxia [21% O2], PC induced an accumulation of hypoxia-inducible transcription factors (HIF) 1α and HIF-2α in a time and concentration [1 µM-2 µM] dependent manner. Here, PC-induced HIF stabilisation was dependent on activation of the PI-3Kinase pathway. This is the first study to demonstrate regulation of the HIF pathway by PC which may have importance in the mechanism underlying renoprotection by PC.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Catherine Godson, Cormac T. Taylor, Aidan Ryan, Cliodhna Cullen, Carsten C. Scholz, Eoin P Brennan, Karen A Nolan

Experts in our system

1
Catherine Godson
University College Dublin
Total Publications: 93
 
2
Cormac T. Taylor
University College Dublin
Total Publications: 110
 
3
Carsten C Scholz
University College Dublin
Total Publications: 21
 
4
Eoin P Brennan
University College Dublin
Total Publications: 18
 
5
Karen A Nolan
University College Dublin
Total Publications: 4