T2 Nanomedicina

Overexpression of this protein in 60% of the ccRCCs has already been described. HAVR/KIM-1 overexpression in human ccRCC cell lines blocks cell differentiation and promotes cell scattering. We aim to determine the role of HAVR/KIM-1 in the development and progression of ccRCC, and its possible value as a diagnostic and prognostic biomarker.

We also focus on KIM-1’s role in ischemia/reperfusion- or nephrotoxic-induced renal tubular injury. Overexpression of this protein in kidney injury has been described. However, whether its involvement is associated with processes enabling to recover tubular epithelium or potentially increasing damage is not known to this date. With the assistance of cultured renal tubular cell models, we are now investigating whether KIM-1 expression shifts are correlated with renal proximal tubule regeneration ability and, as a consequence, investigating its potential therapeutic application.

Among the genes identified in our laboratory that are kidney-specific and regulated by androgens at the transcriptional level we are particularly focused on the one that codes for the kidney androgen-regulated protein (KAP). Besides characterization of  the functional promoter elements that enable KAP expression in proximal tubule epithelial cells, we have generated a transgenic (Tg) mouse model that overexpresses KAP in proximal tubule cells under the presence of androgens, in order to mimick the endogenous KAP expression pattern. KAP Tg mice show altered lipid metabolism, glycosuria, proteinuria and hypertension, as well as focal segmental glomerulosclerosis mediated by increased oxidative stress. We are currently working in this Tg model and also preparing conditional knock-out mice to further caharacterize the role of KAP in renal pathophysiology.

Chronic allograft nephropathy (CAN) is one of the major causes of graft loss in kidney-transplanted patients. The pathogenetic mechanisms of CAN are probably multifactorial, including early noxious agents as a consequence of  ischemia / reperfusion of the graft or high loading doses of anticalcineurinics (aCN), and also chronic damage following aCN therapy, rejection or other reasons. We want to determine the proteomic and genomic changes occurring in tubular cells after different noxious agents (cyclosporin, tacrolimus, other renal toxicants, hypoxia), and also the effects caused by immunophilin silencing (anticalcineurin receptors) in the renal proximal tubule cells. Our objective is to identify specific markers of kidney injury that would be useful to anticipate toxicity or injury in early starges. Those putative markers will be clinically validated in collaboration with the Nephrology and the Pathology services of Vall d’Hebron Hospital.

Idiopathic nonfamilial focal segmental glomerulosclerosis (FSG) is a disease with no treatment, whose usual outcome is end-stage renal disease frequently recidivating after transplantation. In close cooperation with the Nephrology and Paediatric Nephrology services of  Vall d'Hebron hospital together with hospitals throughout the country that provide a significant number of patients, we intend to identify the hypothetical blood factor that causes the proteinuria observed in this disease. Identification of such plasma factor, by means of differential proteomic analysis, would allow the definition of therapeutic targets for the disease, which currently lacks an effective treatment. Our second objective is to find biomarkers that enable us to foresee a potential recidivation and the consequent loss of the graft following renal transplantation to FSG patients.