Diabetologie und Stoffwechsel 2015; 10 - FV20
DOI: 10.1055/s-0035-1549526

Loss of ALCAM/CD166 partially protects against diabetic nephropathy

R von Bauer 1, A Sulaj 2, S Kopf 2, E Gröne 3, HJ Gröne 3, S Hoffmann 4, E Schleicher 4, HU Häring 5, V Schwenger 6, S Herzig 7, PP Nawroth 2, T Fleming 2
  • 1SRH Klinikum Karlsbad-Langensteinbach, Department of Internal Medicine, Karlsbad, Germany
  • 2University of Heidelberg, Department of Medicine I and Clinical Chemistry, Heidelberg, Germany
  • 3German Cancer Research Center, Division of Cellular and Molecular Pathology, Heidelberg, Germany
  • 4University of Heidelberg, Medical Research Center, Medical Faculty Mannheim, Mannheim, Germany
  • 5University of Tübingen, Department of Internal Medicine, Tübingen, Germany
  • 6University of Heidelberg, Department of Nephrology, Heidelberg, Germany
  • 7German Cancer Research Center DKFZ, Network Aging Research, ZMBH, Joint Research Division, Molecular Metabolic Control, Heidelberg, Germany

Introduction/Background: Activated leukocyte cell adhesion molecule (ALCAM/CD166) has been shown to function as a pattern recognition receptor, analogue to the receptor of advanced glycation endproducts. In this study role of ALCAM in diabetic nephropathy was investigated in patients with type 2 diabetes, and further investigated in vitro and in vivo using homozygous knock-out mice for ALCAM (ALCAM-/-).

Materials and methods: The serum concentration of soluble ALCAM (sALCAM), as well the expression of ALCAM and its major ligand, S100B in the kidney was determined in patients with type 2 diabetes. In vivo, diabetes was induced by low-dose streptozotocin in wild-type and ALCAM-/- mice which were assessed for symptoms of DN and expression of ALCAM.

Results: sALCAM concentration was significantly increased in type 2 diabetes patients, and correlated positively with HbA1c, as well as the extent of chronic kidney disease and negatively correlated with estimated glomerular filtration rate. In the kidneys of type 2 diabetes patients, ALCAM was up-regulated in both the glomeruli and proximal and distal tubules. In contrast, S100B was significantly increased in the glomeruli, especially in the podocytes, but not in the tubules. In mice, ALCAM was also localized to the glomeruli and tubules, whereas S100B was only localized to the tubules. It was found that diabetic ALCAM-/- mice were partially protected against nephropathy.

Conclusions: ALCAM was increased in serum and kidneys of type 2 diabetic patients and S100B-induced expression of TGF-ß in vitro was dependent on ALCAM under diabetes, therefore describing a novel mechanism on the late complications of diabetes in the kidney.