Complication of diabetes
Despite the evidence that both type 1 and type 2 diabetes are presently treated with up to date therapeutic protocols, normalization of glycemic control appears to be still out of reach. The gap existing between the “ideal” cure still to come and the present pharmacological treatment of diabetes is the cause of the development of life-threatening diabetic complications such as nephropathy and retinopathy. The hypothesis of this unit is that glucose toxicity represents a compelling challenge for progenitor cells of organs such as the renal glomerulus or the retina known as the major targets of diabetes.
If Complication of diabetes Unit will be able to identify and take advantage of these progenitors, researchers will also have in their hands a powerful cellular tool for contrasting and, at least potentially, reversing, the chronic complications induced by diabetes.
- New approaches to prevent and cure the microvascular complications (retinopathy and nephropathy) of diabetes. Despite the evidence that therapeutic protocols for both type 1 and type 2 diabetes have been greatly improved, the percentage of patients developing end stage renal disease and proliferative diabetic retinopathy remains very high, suggesting that new ways to treat and prevent these complications are needed. To reach this aim, the unit presently working on two parallel projects.
- Identification of the mechanisms leading to pathologic podocyturia in diabetic nephropathy. Inside the renal glomerulus, the podocyte is the cell responsible for the size-selectivity of the glomerular filtration barrier (the reason why albumin and, in general, serum proteins do not usually reach the urine). Recent evidences suggest that a small number of podocytes is lost with urine in normal subjects, so called “physiologic podocyturia”. The number greatly increases in case of diabetic nephropathy and this phenomenon could be directly involved in its pathogenesis. The group has recently set up a new technique to identify and characterize urinary podocytes. The comprehension of the diabetes-induced mechanisms leading to podocyte detachment and loss with urine could represent a key point toward the setting-up of a successful preventive strategy for diabetic nephropathy.
- Role of endothelial progenitor cells in the pathogenesis of diabetic retinopathy. The proliferation inside the retina of new, leaky capillaries causing hemorrhages and retinal detachment represents the worst consequence of the development of diabetic retinopathy (so called proliferative diabetic retinopathy). It has been recently demonstrated that bone marrow-derived endothelial progenitor cells take part in the pathogenesis of proliferative retinopathy in man. A phenomenon that suggests, on one hand, that the cells involved in the pathogenesis of proliferative retinopathy originate (at least in part) from outside the retina (the bone marrow) and, on the other, that it should be possible to prevent/treat this complication by modulating the number and/or the activity of circulating endothelial progenitor cells. To reach this goal, this groups is involved in studies aimed to verify the possibilty to control the intraretinal homing of endothelial progenitor cells through the pharmacological targeting of cytokines involved in cell adhesion. The results of this study could allow to set up a new therapeutic approach for both prevention and cure of diabetic retinopathy.
Paterniti I, Di Paola R, Campolo M, Siracusa R, Cordaro M, Bruschetta G, Tremolada G, Maestroni A, Bandello F, Esposito E, Zerbini G, Cuzzocrea S. Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2015 Dec 15;769:313-23.
Maestroni S, Maestroni A, Ceglia S, Tremolada G, Mancino M, Sacchi A, Lattanzio R, Zucchiatti I, Corti A, Bandello F, Zerbini. Effect of chromogranin A-derived vasostatin-1 on laser-induced choroidal neovascularization in the mouse. G. Acta Ophthalmol. 2015 May;93(3):e218-22.
Maestroni S, Maestroni A, Dell’Antonio G, Gabellini D, Terzi S, Spinello A, Meregalli G, Castoldi G, Zerbini G. Viable podocyturia in healthy individuals: implications for podocytopathies. Am J Kidney Dis. 2014 Dec; 64(6):1003-5.
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Sandholm N, Forsblom C, Mäkinen VP, McKnight AJ, Osterholm AM, He B, Harjutsalo V, Lithovius R, Gordin D, Parkkonen M, Saraheimo M, Thorn LM, Tolonen N, Wadén J, Tuomilehto J, Lajer M, Ahlqvist E, Möllsten A, Marcovecchio ML, Cooper J, Dunger D, Paterson AD, Zerbini G, Groop L; SUMMIT Consortium, Tarnow L, Maxwell AP, Tryggvason K, Groop PH; FinnDiane Study Group. Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes. Diabetologia 2014 Jun;57(6):1143-53.
Tremolada G, Del Turco C, Lattanzio R, Maestroni S, Maestroni A, Bandello F, Zerbini G. The role of angiogenesis in the development of proliferative diabetic retinopathy: impact of intravitreal anti-VEGF treatment. Exp Diabetes Res. 2012. 2012:728325.
Zerbini G, Maestroni A, Palini A, Tremolada G, Lattanzio R, Maestroni S, Pastore MR, Secchi A, Bonfanti R, Gerhardinger C, Lorenzi M. Endothelial progenitor cells carrying monocyte markers are selectively abnormal in type 1 diabetic patients with early retinopathy. Diabetes 2012 Apr; 61(4): 908-914.
Zerbini G, Bonfanti R, Meschi F, Bognetti E, Paesano PL, Gianolli L, Querques M, Maestroni A, Calori G, Del Maschio A, Fazio F, Luzi L, Chiumello G. Persistent renal hypertrophy and faster decline of glomerular filtration rate precede the development of microalbuminuria in type 1 diabetes. Diabetes 2006. 55:2620-2625.
Zerbini G, Piemonti L, Maestroni A, Dell’Antonio G, Bianchi G. Stem cells and the kidney, a new therapeutic tool? J Am Soc Nephrol. 2006 Apr;17(4 Suppl 2):S123-6.
Asnaghi V, Lattanzio R, Mazzolari G, Pastore MR, Ramoni A, Maestroni A, Ruggieri D, Luzi L, Brancato R, Zerbini G. Increased clonogenic potential of circulating endothelial progenitor cells (EPCs) in patients with type 1 diabetes and proliferative retinopathy. Diabetologia 2006 May; 49 (5):1109-1111.