Carlos Vío

Investigación

Fibrosis and Progression of Chronic Renal Diseases and Hypertension

The fibrotic disorders characterize for an excessive scar tissue accumulation, that replacing the normal tissue, causes the malfunctioning of tissues and organs. Most chronic diseases, with damage and repair cycles, are associated with fibrosis. In the case of the hypertension, phenomenon that reaches 20 % of the population, the renal fibrosis is a characteristic of this disease. The CARE will investigate new drugs and active products, like renal fibrosis inhibitors, focusing the work in a basic, as well as an applied level, in the renal pathology study in animal models and cells culture.

In diabetic and non-diabetic nephropathies, as well as in other renal diseases, the degree of chronic kidney failure and its rate of progression correlate with tubulointerstitial fibrosis. Progressive fibrosis then leads to tissue scarring with destruction of organ architecture. Angiotensin II is a main contributor to the progressive renal fibrosis, through mechanisms involving chemotactic factors (MCP-1, osteopontin), profibrotic growth factors (TGF-β, CTGF), recruitment of macrophages and myofibroblasts, and ECM production. We have provided evidence for a nephropatic role of the Angiotensin Converting Enzyme (ACE), which controls the local activity of the renin angiotensin and kallikrein kinin systems. There is evidence suggesting that other hormones, such as Angiotensin 1-7 (Ang 1-7), Bradykinin and Cyclooxygenase-2 (COX-2) derived prostaglandins (PGI2, PGE2), may counteract the profibrotic effect of Angiotensin-II. Furthermore, we have observed a decreased COX-2 expression in model of renal fibrosis, suggesting it plays a role in the pathogenic mechanisms of fibrosis progression.

Objetivs:

• To study the role of Ang 1-7 and COX-2-derived prostaglandins in the onset and progression of fibrosis in kidney and muscle
• The role of pro-fibrotic cytokines TGF-β and CTGF in the kidney