#55 The role of integrin a3ß1 in the development of morphological changes in renal tissue in patients with diabetic nephropathy

Abstract Background and Aims Diabetic kidney disease (DKD) is a common microvascular complication and a major cause of renal failure in patients with diabetes mellitus. DKD is a type of kidney disease that harms the glomerular filtration barrier. This barrier is made up of three parts: fenestrated endothelial cells, the glomerular basement membrane, and podocytes. Progression of DKD affects podocyte structure and leads to foot process effacement. Podocyte damage and loss plays a major role in the development and final progression of DKD. Podocytes are terminally differentiated cells, which is why their loss is a key factor contributing to the progression of DKD. The main podocyte receptor involved in attachment to the GBM is the alpha3beta1 integrin. Loss or reduction of α3β1 integrin can lead to detachment of podocytes from the glomerular basement membrane (GBM). In the absence of α3β1, disorganization of the GBM occurs. The aim of the study is to investigate the role of alpha3beta1 integrin expression in renal tissue in patients with type 2 diabetes with different morphological classes of diabetic nephropathy (DN) and to assess its impact on the development and progression of histological changes in renal tissue. Method The study included 50 patients with type 2 diabetes complicated by diabetic nephropathy. The average age was 66.58 ± 3.27 years. There were 35 women and 14 men. The disease duration in patients with diabetes was 17.70 ± 0.35 years. The duration of DN from the detection of microalbuminuria to the morphological examination of the renal tissue and diagnosis was 1.65 ± 0.34 years. According to light microscopy, class IIa was detected in 12 patients, class IIb in 14 patients, class III in 19 patients, and class IV in 5 patients. According to the results of light microscopy, no signs of glomerulonephritis were found in any of the patients. In addition to light microscopy, the expression of integrin alpha3beta1 in the GBM and mesangial cells was determined in all patients. Results It was shown that α3β1 expression in the renal tissue of patients with type 2 diabetes mellitus is detected in the area of ​​the glomerular basement membrane (1.400 ± 0.364 Me = 1.264 (95% CI: 0.700–2.100)) and mesangial cells (0.851 ± 0.145 Me = 1.042 (95% CI: 0.574–1.148)). The highest levels of α3β1 expression were found in patients with class IIa DN. As the disease progressed to class IV, the levels of α3β1 expression decreased significantly (P = 0.001) (Fig. 1). Correlation analysis showed reliable associations of α3β1 expression in GBM with the development of nodular lesions (R = −0.358 р = 0.014) and segmental sclerosis (R = 0.437 р = 0.002), and expression in mesangial cells - with the expansion of the mesangial matrix (R = 0.303 р = 0.039) and segmental sclerosis of renal tissue (R = 0.614 р = 0.000). Regression analysis showed a relationship between alpha3beta1 expression in mesangial cells and the development of segmental sclerosis (R2 = 0.377 F = 27.21 β = 0.614 P = 0.000). Conclusion The expression level of α3β1 in the glomerular basement membrane and mesangial cells plays a role in the mechanism of morphological tissue damage. Therefore, the loss of podocytes in diabetes mellitus acts as a major participant in the glomerulosclerotic process.