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

Abstract

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.

New insights into RAGE/Diaph1 interaction as a modulator of actin cytoskeleton dynamics in peripheral nervous system in long‐term hyperglycaemia

“…Our earliest studies revealed a decreased number of myelinated axons in diabetic models (Jaroslawska et al, 2021; Juranek, Geddis, Roasario, & Schmidt, 2013). However, the expression of beta actin did not differ in sciatic nerve harvested from diabetic and control group (Jaroslawska et al, 2021; Zglejc‐Waszak et al, 2022).…”

“…In silico analysis revealed that in diabetic sciatic nerve the most enriched biological pathway was that one related to the regulation of actin cytoskeleton (mmu04810, Zglejc‐Waszak et al, 2022). This phenomenon may suggest that actin cytoskeleton may play an essential role in therapeutic strategy to prevent perturbations in diabetic peripheral nerves.…”

Novel insights into RAGE signaling pathways during the progression of amyotrophic lateral sclerosis in RAGE-deficient SOD1 G93A mice

“…We can speculate that the deletion of RAGE in ALS mice may inhibit progression of astroglia activation and gliosis during disease [32]. Moreover, we can hypothesize that the deletion of RAGE in ALS mice may inhibit progression of neurodegeneration and motor neuron damage (Fig 6) [7,15,23,32,37]. However, pathological mechanism of ALS is still not well known and poorly understood [1,6,21,22,35,36,26,[38][39][40][41].…”