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Expression of receptor for advanced glycation end-products and its ligands HMGB 1 and s 100A 12 in children and adolescents with new-onset Type 1 diabetes and in patients with longer disease duration (CROSBI ID 685607)

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Spehar Uroic, Anita ; Krnic, Nevena ; Svigir, Alen ; Rojnic Putarek, Natasa Expression of receptor for advanced glycation end-products and its ligands HMGB 1 and s 100A 12 in children and adolescents with new-onset Type 1 diabetes and in patients with longer disease duration // Hormone Research in Paediatrics. 2019. str. 144-145

Podaci o odgovornosti

Spehar Uroic, Anita ; Krnic, Nevena ; Svigir, Alen ; Rojnic Putarek, Natasa

engleski

Expression of receptor for advanced glycation end-products and its ligands HMGB 1 and s 100A 12 in children and adolescents with new-onset Type 1 diabetes and in patients with longer disease duration

Background: Receptor for advanced glycation end- products (RAGE) is a multiligand receptor up- regulated at sites of inflammation, especially in tissues with accelerated advanced glycation end-products formation. It is additionally stimulated by RAGE ligands S100A12 and HMGB1 released from recruited immune cells thus perpetuating the inflammatory process with a potential role in the development of type 1 diabetes as well as in development in diabetes complications. Expression of RAGE molecules and its ligands has not been evaluated in new-onset diabetic patients, and data on their role in diabetes development are still scarce. Aim: To assess gene expression for RAGE, S100A12 and HMGB1 in peripheral blood mononuclear cells (PBMC) and plasma concentration of truncated receptor sRAGE and CRP in patients suffering from new-onset type 1 diabetes (NT1D), in patients with disease duration of more than five years (T1D) and in healthy controls. Subjects and Methods: We included 35 NT1D patients (47.5% female, age 10.7+/-3.0 years), 36 T1D patients (47.2% female, age 16.3+/-5.6 years), and 36 healthy controls (55.6% female, age 16.2+/-6.9 years). Gene expression for RAGE, S100A12, and HMGB1 was quantified using qPCR, and sRAGE level was measured by ELISA. CRP was measured by routine laboratory method. Results: The PBMC s100A12 gene expression (in arbitrary units, AU) was significantly lower in NT1D patients compared to controls (mean ±SD (95%CI) = 1.22±0.81 (0.94-1.51) v.s. 2.62 (2.01-3.23), p=0.040) and compared to T1D (3.07±3, 10 (2.02- 4.12), Poster Category 1 Horm Res Paediatr 2019 ; 91(suppl 1):1–682 DOI: 10.1159/000501868 145 p=0.002). HMBG (AU) expression was also lower in NT1D when compared to controls (0.73±0.63 (0.51- 0.95) v.s. 1.91 (0.97-1.42), p=0.031) with no difference when compared to T1D. There was no difference between groups neither in RAGE gene expression nor in plasma sRAGE levels. NT1D also showed higher CRP (mg/dL) levels when compared to control group (2, 32±4, 15 (0, 77-3, 87) v.s. 0, 62±0, 95 (0, 27-0, 96), p=0.023). Conclusion: Our findings might suggest the role of s100A12 and HMGB1 in type 1 diabetes development. However, we expected increased expression of these molecules in the setting of enhanced inflammation as suggested by higher CRP levels. We speculate that s100A12 and HMGB1 expression might be restricted to sites of inflammation harvesting PBMC expressing these genes from peripheral blood. Comparison between gene and protein expression in peripheral blood as well as between circulation and affected tissues should be performed in order to explain the contribution of these molecules to the development of diabetes

type 1 diabetes, RAGE, alarmins

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Podaci o prilogu

144-145.

2019.

nije evidentirano

objavljeno

Podaci o matičnoj publikaciji

Hormone Research in Paediatrics

Karger Publishers

3-318-06601-2

1663-2818

1663-2826

Podaci o skupu

58th Annual ESPE Meeting (ESPE 2019)

poster

19.09.2019-21.09.2019

Beč, Austrija

Povezanost rada

Kliničke medicinske znanosti

Indeksiranost