RAS IN ECM SYNTHESIS · Involvement of RAS signalling in TGF-ss1-mediated extracellular matrix synthesis relathionship between TGF-ss1 and angiotensin II
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-01-20 → 2005-01-19
- EU contribution
- €28,551
- Participants
- 1
- Scheme
- ERG
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Results in brief
Final Activity Report Summary - RAS IN ECM SYNTHESIS (Involvement of RAS signalling in TGF-ss1-mediated extracellular matrix synthesis Relathionship between TGF-ss1 and angiotensin II)
Fibrosis and extracellular matrix (ECM) synthesis is a common end-stage in pathologies like diabetes and hypertension, with a high incidence in the European Union. We studied the involvement of Ras proteins in ECM synthesis induced by transforming growth factor beta, the role of the different Ras isoforms in fibrosis, and the intracellular pathways involved in this process. Ras proteins seem to be involved in extracellular matrix synthesis in fibroblasts. The absence of N and H-Ras increase ECM synthesis in fibroblasts, as well as decreases the proliferative rate of this cell type. Moreover, in an in vivo model of experimental renal fibrosis, the expression of Ras is increased.
Data: CORDIS, © European Union
Project objective
Systemic hypertension is one of the most prevalent diseases among the population of our country, and it also has a very big social and economic repercussion. Renal injury is one of its most important complications, and it is also one of the main sources of chronic renal insufficiency. Uncontrolled hypertension damages renal function by two basic mechanisms: intraglomerular hypertension and renal hypertrophy, leading to glomerular sclerosis by a common mechanism involving the action of autocrine or paracrine mediators like angiotensin II (All) and transforming growth factor ÿ1 (TGF-ÿ1 ). TGF-ÿ1 is very important in the mediation of this process, due to its role in the regulation of cellular proliferation, and also in the synthesis and degradation of extracell ular matrix (ECM). This cytokine seems to have an important role in the induction and development of interstitial fibrosis; its sustained expression induces chronic and progressive tissular fibrosis. TGF-ÿ systemic administration causes an elevation of the tissue levels of All, that also induces interstitial fibrosis in mesangial cells and in nephron tubular epithelium, causing ECM accumulation; moreover, All induces TGF-ÿ1 synthesis in mesangial cells, proximal tubule epithelial cells and vascular smooth m uscle cells. TGF-ÿ1 induces the expression of the prooncogenic GTPase Ras, and both molecules cooperate synergically in the progression of undifferentiated invasive tumours. TGF-ÿ1 enhances significantly the Ras mitogenic effects. However, Ras can also inh ibit cellular hypertrophy and ECM synthesis induced by TGF-ÿ1 signalling. Both TGF-ÿ1 and All induce the expression of connective tissue growth factor (CTGF), hypertrophie cytokine that maintains cells in d phase of the cell cycle. CTGF may be a mediator o f the profibrotic effects induced by TGF-ÿ. The aim of this project is the analysis of TGF-ÿ1 mediation in All-induced ECM synthesis, the possible implication of Ras #
Original text from CORDIS.
Participants
- UNIVERSIDAD DE SALAMANCA · SALAMANCACoordinatorSpain
Links
Data: CORDIS, © European Union