DMMC Course: MOLECULAR CELL BIOLOGY IN ACTION

1110-1230 Wednesday 16 November 2005. UCD Conway Institute Lecture Theatre

TGF-beta1 signalling and its role in promoting chronic renal damage
Dr Neil G. Docherty (UCD Conway Institute of Biomolecular & Biomedical Research)

Transforming growth factor-beta (TGF-beta1) is the key member of the transforming growth factor superfamily implicated in diverse aspects of pathophysiological remodelling during both acute and chronic renal disease.

This lecture aims firstly to describe the basic molecular biology of TGF-beta1 including the activation of its major intracellular signalling cascade, the Smad pathway. The lecture will then focus on how TGF-beta1 expression and activity can be activated in the acutely injured kidney, using information from both in vitro and in vivo models. An examination of the subsequent effects of this increased activity on both the apoptotic and fibrotic responses will be made and related to chronic renal remodelling and loss of function. Reflecting our research interest, particular focus will be given to the role of TGF-beta1 in promoting epithelial-mesenchymal transdifferentation in injured areas of the tubular epithelium.

Lastly, the lecture will illustrate how the antagonism of TGF-beta1 activity in animal models of acute renal injury can protect against long term pathophysiological changes, thus highlighting TGF-beta1 activity as a key target in preventing long-term renal damage.