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Molecular Medicine

Laboratory of Pathophysiology of Experimental Renal Disease and Interaction with other Organs

Head
Carlamaria
Zoja
Head of Department
Molecular Medicine
carlamaria.zoja@marionegri.it
Senior Advisor
No items found.

The laboratory has developed experimental models of renal diseases, which accurately reproduce clinical and histopathological features of human nephropathies.

The aim is to investigate mediators and molecular mechanisms responsible for the progression to end-stage renal disease and to identify strategies able to slow down or even halt it.

The laboratory has expertise in pathology, immunopathology and molecular biology techniques to be applied to the study of kidney and other organs.

RESEARCH AREAS

Development of experimental models

During the last year, the laboratory has set up a new model of rapidly progressive autoimmune glomerulonephritis, one of the most serious renal diseases that causes terminal organ failure. The current therapy is based on immunosuppressive drugs, which, in addition to causing important side effects, often result ineffective or associated with relapses. The study of this experimental model allowed the characterization of the glomerular cell populations involved in the formation of “crescents”, the typical lesions of this pathology, and to design new pharmacological approaches, whose efficacy is being evaluated.

New therapeutic approaches for diabetic nephropathy

ACE inhibitors are the current gold standard therapy for diabetic nephropathy. However, these drugs may provide imperfect renoprotection, particularly if treatment starts at an advanced stage of the disease. Therefore, it is important to identify new and more effective molecules. In a mouse model of type II diabetic nephropathy, the laboratory has noticed for the first time that the treatment with the stable lanthipeptide cyclic angiotensin 1-7 was able to limit albuminuria, renal injury, inflammation and fibrosis. Combined administration of cyclic angiotensin 1-7 and ACE inhibitor exerted an antiproteinuric and renoprotective effect, even superior to that observed after the standard therapy with the ACE inhibitor alone, suggesting the importance of this combined therapy for the cure of diabetic nephropathy.

Strategies to inhibit complement activation

Membranoproliferative glomerulonephritis (MPGN) is a rare renal pathology associated to complement system activation and characterized by proteinuria and chronic renal insufficiency. The laboratory has available deficient mice for factor H, a regulatory protein of the complement system, which spontaneously develop MPGN. The resulting aberrant activation of complement proteins leads to decreased levels of circulating C3 and to the accumulation of C3 deposits in the kidney. It is under evaluation the efficacy of the treatment with small interfering RNA (siRNA) for complement factors. These molecules are able to specifically inhibit the production of complement proteins by the liver.

Sodium-glucose cotransporter 2 (SGLT2) inhibition in renal diseases

SGLT2 inhibitors are drugs approved for the treatment of type 2 diabetes that beyond blood glucose lowering effects, display renoprotective effects in diabetic kidney disease. Recently, the laboratory has demonstrated the efficacy of these drugs even in a mouse model of non-diabetic nephropathy induced by protein overload. SGLT2 inhibition limited proteinuria and ameliorated dysfunction and loss of podocytes, cells that are crucial to maintain an intact glomerular filtration barrier. For the first time, it has been shown that podocytes express SGLT2, whose levels rise in condition of glomerular damage. Studies are ongoing to further elucidate the mechanisms underlying the renoprotective effects of SGLT2 inhibition.

Head Unit
Daniela
Corna
Head Unit
daniela.corna@marionegri.it
Mauro
Abbate
Head Unit
mauro.abbate@marionegri.it
Staff
Cristina
Zanchi
Researcher
cristina.zanchi@marionegri.it
Daniela
Rottoli
Researcher
daniela.rottoli@marionegri.it
Monica
Locatelli
Researcher
monica.locatelli@marionegri.it
Domenico
Cerullo
Researcher
domenico.cerullo@marionegri.it
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Codice:

International Consensus on Cardiopulmonary Resuscitation.

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Head
Carlamaria
Zoja
Head of Department
Molecular Medicine
carlamaria.zoja@marionegri.it
Senior Advisor
No items found.

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