Proteomic profiling of whole-saliva reveals correlation between Burning Mouth Syndrome and the neurotrophin signaling pathway

Guy Krief,Aaron Palmon,Doron J Aframian,Yaron Haviv,Batia Zacks,Galit Almoznino,Omer Deutsch,Naama Keshet

doi:10.1038/s41598-019-41297-9

Guy Krief, Aaron Palmon + Show 6 more

Open Access

https://doi.org/10.1038/s41598-019-41297-9

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Abstract

Burning mouth syndrome (BMS) is characterized by a spontaneous and chronic sensation of burning in the oral mucosa, with no apparent signs. The underlying pathophysiological and neuropathic mechanisms remain unclear. Here, we attempt to elucidate some of these mechanisms using proteomic profiling and bioinformatic analyses of whole-saliva (WS) from BMS patients compared to WS from healthy individuals. Qualitative and quantitative proteomic profiling was performed using two dimensional gel electrophoresis (2-DE) and quantitative mass spectrometry (q-MS). In order to improve protein visibility, 21 high abundance proteins were depleted before proteomic profiling. Quantitative proteomic analysis revealed 100 BMS specific proteins and an additional 158 proteins up-regulated by more than threefold in those with BMS. Bioinformatic analyses of the altered protein expression profile of BMS group indicated high correlations to three cellular mechanisms including the neurotrophin signaling pathway. Based on this finding, we suggest that neurotrophin signaling pathway is involved in the pathophysiology of BMS by amplifying P75NTR activity, which in turn increases neural apoptosis thereby reducing sub-papillary nerve fiber density in the oral mucosa.

Highlights

The diagnosis of burning mouth syndrome (BMS) is based on an intraoral burning or dysaesthetic sensation, recurring for more than two hours per day for at least 3 months, without clinically visible causative lesions.[1,2]
We employed qualitative and quantitative proteomic approaches, coupled with bioinformatic analyses of WS from Burning mouth syndrome (BMS) patients to increase our understanding of this condition
In order to obtain high proteomic resolution for sensitive detection of low abundance proteins, 21 High abundance proteins (HAP) were depleted from the samples including the most abundant WS proteins sAA and Alb

Summary

Introduction

The diagnosis of burning mouth syndrome (BMS) is based on an intraoral burning or dysaesthetic sensation, recurring for more than two hours per day for at least 3 months, without clinically visible causative lesions.[1,2]. Further bioinformatic analyses our understanding of the pathophysiology of diseases including BMS may improve[22,23]. 3,000 proteins have been identified in WS24 and proteomic profiling demonstrated altered protein expression in oral diseases such as oral squamous cell carcinoma[25], Sjögren’s syndrome[18], periodontitis[26] as well as in neurological conditions such as Alzheimer disease[27] and other central nervous system (CNS) diseases[28]. High abundance proteins (HAP), hamper proteomic analysis of WS, as previously described[29,30,31]. These highly expressed proteins include salivary alpha www.nature.com/scientificreports/. Unique clusters of protein complexes were detected, correlating with the involvement of neuropathic mechanisms in BMS

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