Transforming Growth Factor-ß1 and Receptor for Advanced Glycation End Products Gene Expression and Protein Levels in Adolescents with Type 1 Diabetes Mellitus
Ana Ninic1, Dragana Bojanin2, Miron Sopic1, Marija Mihajlovic1, Jelena Munjas1, Tatjana Milenkovic3, Aleksandra Stefanovic1, Jelena Vekic1, Vesna Spasojevic-Kalimanovska11University of Belgrade Faculty of Pharmacy, Department for Medical Biochemistry, Belgrade, Serbia2Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”, Biochemical Laboratory, Belgrade, Serbia
3Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”, Department of Endocrinology, Belgrade, Serbia
Objective: Type 1 diabetes (T1D) mellitus is one of the most frequent autoimmune diseases in childhood. Chronic complications are the main causes of cardiovascular morbidity and mortality in T1D. Although interactions between advanced glycation end products (AGE) and their receptors (RAGE) and transforming growth factor-ß1 (TGF-ß1) are implicated in development and progression of diabetic microand macro-vascular complications, they also have important roles in immune system regulation.
Methods: Blood samples were obtained from 156 adolescents with T1D and 80 apparently healthy controls. T1D patients diagnosed with any other autoimmune disease and receiving any kind of drugs except insulin therapy were excluded from this study. Exclusion criteria for controls were positive family history of T1D and drugs/supplements application. TGF-ß1 and transmembrane full-length RAGE (flRAGE) messenger ribonucleic acid (mRNA) levels in peripheral blood mononuclear cells (PBMC) were obtained by quantitative polymerase chain reaction (qPCR) method. Circulating levels of biochemical markers, TGF-ß1 and soluble RAGE (sRAGE) levels were also determined.
Results: TGF-ß1 and flRAGE mRNA levels were significantly higher in controls compared to patients (p<0.001, for both). However, TGF-ß1 and sRAGE levels were higher in patients than controls (p<0.001, for both). There were significant independent associations of all mRNA and protein levels with T1D. TGF-ß1 mRNA was the only marker independently negatively associated with urinary albumin excretion rate in T1D adolescents (p=0.005).
Conclusion: Our results indicated gene expression downregulation of TGF-ß1 and flRAGE in PBMC of T1D adolescents. TGF-ß1 mRNA downregulation may be useful for predicting early elevation of urinary albumin excretion rate.
Manuscript Language: English
