Modulation of tissue transglutaminase in tubular epithelial cells alters extracellular matrix levels: a potential mechanism of tissue scarring

The up-regulation and trafficking of tissue transglutaminase (TG2) by tubular epithelial cells (TEC) has been implicated in the development of kidney scarring. TG2 catalyses the crosslinking of proteins via the formation of highly stable e(?-glutamyl) lysine bonds. We have proposed that TG2 may contribute to kidney scarring by accelerating extracellular matrix (ECM) deposition and by stabilising the ECM against proteolytic decay. To investigate this, we have studied ECM metabolism in Opossum kidney (OK) TEC induced to over-express TG2 by stable transfection and in tubular cells isolated from TG2 knockout mice. Increasing the expression of TG2 led to increased extracellular TG2 activity (p < 0.05), elevated e(?-glutamyl) lysine crosslinking in the ECM and higher levels of ECM collagen per cell by 3H-proline labelling. Immunofluorescence demonstrated that this was attributable to increased collagen III and IV levels. Higher TG2 levels were associated with an accelerated collagen deposition rate and a reduced ECM breakdown by matrix metalloproteinases (MMPs). In contrast, a lack of TG2 was associated with reduced e(?-glutamyl) lysine crosslinking in the ECM, causing reduced ECM collagen levels and lower ECM per cell. We report that TG2 contributes to ECM accumulation primarily by accelerating collagen deposition, but also by altering the susceptibility of the tubular ECM to decay. These findings support a role for TG2 in the expansion of the ECM associated with kidney scarring.

Local economic development initiatives and the transition from training and enterprise councils to new institutional structures in England

Current British government economic development policy emphasises regional and sub-regional scale, multi-agent initiatives that form part of national frameworks to encourage a 'bottom up' approach to economic development. An emphasis on local multi-agent initiatives was also the mission of Training and Enterprise Councils (TECs). Using new survey evidence this article tracks the progress of a number of initiatives established under the TECs, using the TEC Discretionary Fund as an example. It assesses the ability of successor bodies to be more effective in promoting local economic development. Survey evidence is used to confirm that many projects previously set up by the TECs continue to operate successfully under new partnership arrangements. However as new structures have developed, and policy has become more centralized, it is less likely that similar local initiatives will be developed in future. There is evidence to suggest that with the end of the TECs a gap has emerged in the institutional infrastructure for local economic development, particularly with regard to workforce development. Much will depend in future on how the Regional Development Agencies deploy their growing power and resources.