Targeting Cellular Drivers and Counter-regulators of Hyperglycaemia and TGF-ß1
Associated Pro-fibrotic Responses in Diabetic Kidney Disease.
Authors Docherty NG, Murphy M, Martin F, Brennan EP, Godson C
Submitted By Catherine Godson on 8/5/2014
Status Published
Journal Experimental physiology
Year 2014
Date Published 8/1/2014
Volume : Pages 99 : 1154 - 1162
PubMed Reference 25085843
Abstract Diabetic Kidney Disease (DKD) occurs in upwards of 30% of patient with type 2
diabetes mellitus (T2DM) and is characterised at source by a maladaptive
response in the renal parenchyma to exposure to a glucotoxic/lipotoxic diabetic
milieu that courses coincident with hypertension. The consequence of these
maladaptive responses is progressive renal injury which is exacerbated by the
development of a chronic inflammatory infiltrate associated with the development
of tubulointerstitial fibrosis. The evolution of tubulointerstitial fibrosis
correlates with the loss of functional renal mass and descent towards renal
failure. Transforming growth factor beta-1 (TGF-ß1) is a recognised mediator of
the pro-fibrotic response of mesangial cells and renal tubular epithelial cells
to hyperglycaemia. While euglycaemia remains the goal in the treatment of T2DM,
prevention, arrest and reversal of microvascular complications such as DKD may
be assisted by pharmacological modulation of the effectors of of glucotoxicity
such as TGF-ß1. This review focuses on describing how through reductionist in
vitro experimentation focusing on TGF-ß1 related responses to hyperglycaemia, we
have identified Induced by High Glucose-1 (IHG-1), Induced by High Glucose-2
(IHG-2/Grem 1) and the lipoxin inducible microRNA let-7c as potential targets
for harnessing new therapeutic approaches to limit the bioactivity of TGF-ß1 in
DKD. This article is protected by copyright. All rights reserved.

Investigators with authorship
Catherine GodsonUniversity College Dublin