The receptor for advanced glycation end products and its ligands’ expression in OVE26 diabetic sciatic nerve during the development of length‐dependent neuropathy

• Published in: Neuropathology 2023-02, Vol.43 (1), p.84-94
• Main Authors: Zglejc‐Waszak, Kamila, Schmidt, Ann Marie, Juranek, Judyta K.
• Format: Article
• Language: English
• Subjects: Actin; Advanced glycosylation end products; Animals; Calcium-binding protein; Cytoskeleton; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1; Diabetic Neuropathies; Diabetic neuropathy; Glycation End Products, Advanced - metabolism; Glycosylation; HMGB1 protein; HMGB1 Protein - metabolism; Immunohistochemistry; inflammation; Ligands; Lysine; Mice; mouse; Nervous system; peripheral neuropathy; Profilin; Protein B; Proteins; RAGE; Receptor for Advanced Glycation End Products - metabolism; S100b protein; Sciatic Nerve
• ISSN: 0919-6544; 1440-1789
• DOI: 10.1111/neup.12852

Type 1 diabetes (T1D) may affect the peripheral nervous system and alter the expression of proteins contributing to inflammation and cellular cytoskeleton dysfunction, in most cases leading to the development of diabetic length‐dependent neuropathy (DLDN). In the present study, we performed immunohistochemistry (IHC) to probe the expression of the receptor for advanced glycation end products (RAGE); its key ligands, high‐mobility group box 1 (HMGB1), S100 calcium‐binding protein B (S100B), and carboxymethyl‐lysine (CML – advanced glycation end products (AGE)); and its cytoplasmic tail‐binding partner, diaphanous related formin 1 (DIAPH1) and associated molecules, beta‐actin (ACTB) and profilin 1 (PFN1) proteins in sciatic nerves harvested from seven‐month old FVB/OVE26 mice with genetically‐mediated T1D. We found that the amount of RAGE, HMGB1, and S100B proteins was elevated in diabetic vs the non‐diabetic groups, while the amount of DIAPH1, ACTB, as well as PFN1 proteins did not differ between these groups. Moreover, our data revealed linear dependence between RAGE and HMGB1 proteins. Interaction criss‐cross of selected sets of proteins in the sciatic nerve revealed that there were connected in a singular network. Our results indicate that T1D may alter expression patterns of RAGE axis proteins and thus contribute to DLDN. The receptor for advanced glycation end products (RAGE) and its ligands' expression in OVE26 diabetic sciatic nerve during the development of length‐dependent neuropathy.