Abstract Number: PB0353
Meeting: ISTH 2020 Congress
Background: Diabetic nephropathy (DN), the primary cause of end-stage renal disease, is a multifactorial disease in which inflammation and angiogenesis play a crucial role. SerpinE2, or protease nexin-1 (PN-1), is a protease inhibitor of the serpin family, expressed by vascular and inflammatory cells, that has a strong antiangiogenic potential.
Aims: To address the role of PN-1 in DN.
Methods: Diabetes was induced in PN-1-/- and WT mice by repeted injections of streptozotocin. Vascularization was studied on kidney sections by isolectin labelling. Arterial flow was measured by Doppler. MK expression was analyzed by immunohistochemistry on kidney cryosections and by RT-PCR on renal cDNA.
Results: PN-1-/- diabetic mice presented histological features of an aggravated nephropathy, compared to WT mice, with higher hypertrophy of glomeruli and greater mesangial expansion. Moreover, renal function was worsened in PN-1-/- diabetic mice compared to WT mice, with much higher urine albumin to creatinine ratio in the absence of PN-1. At the very early stage, diabetes is known to induce an increase of glomerular vascularization. We observed that this increased glomerular vascularization was higher in PN-1-/-– than in WT- diabetic mice. However at later stages, kidney vascularization was conversely significantly reduced in PN-1-/- diabetic mice. Similarly, reduction of arterial flow in response to diabetes was less accentuated in PN-1-/- than in WT kidneys in early diabetes but reached the level observed in WT kidneys in late diabetes.
Midkine (MK) is a growth factor involved in DN that has been shown to be overexpressed in retina and muscle of PN-1-/- mice. Our result evidenced higher MK overexpression in PN-1-/- compared to WT kidneys after diabetes induction that could thus be partly involved in the worsening of DN development in PN-1 deficient mice.
Conclusions: In conclusion, our results indicate that PN-1 may play a protective role in the development of DN, possibly via MK downregulation.
To cite this abstract in AMA style:Idir L, Aymonnier K, Boulaftali Y, Bouton M-, Arocas V. Role of Serpine2 (PN-1) in Diabetic Nephropathy [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/role-of-serpine2-pn-1-in-diabetic-nephropathy/. Accessed January 26, 2022.
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