As a critical molecule in the onset and sustainment of inflammatory response, the receptor for advanced glycation end products (RAGE) has a variety of ligands, such as advanced glycation end products (AGEs), S100/calcium granule protein, and high-mobility group protein 1 (HMGB1). Recently, an increasing number studies have shown that RAGE ligand binding can initiate the intracellular signal cascade, affect intracellular signal transduction, stimulate the release of cytokines, and play a vital role in the occurrence and development of immune-related diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Alzheimer’s disease. In addition, other RAGE signaling pathways can play crucial roles in life activities, such as inflammation, apoptosis, autophagy, and endoplasmic reticulum stress. Therefore, the strategy of targeted intervention in the RAGE signaling pathway may have significant therapeutic potential, attracting increasing attention. In this paper, through the systematic induction and analysis of RAGE-related signaling pathways and their regulatory mechanisms in immune-related diseases, we provide theoretical clues for the follow-up targeted intervention of RAGE-mediated diseases.
BackgroundApple is one of the most popular fruit crops world-wide and its skin color is an important quality consideration essential for commercial value. However, the strategy on genetic breeding for red skin apple and the genetic basis of skin color differentiation is very limited and still largely unknown.ResultsHere, we reported a bud sport mutant of Fuji apple with red skin color and enhanced anthocyanins accumulation. Quantitative SWATH-MS (sequential window acquisition of all theoretical spectra-mass spectrometry) proteomics investigations revealed proteome changes in the apple red skin bud mutation and a total of 451 differentially expressed proteins were identified in apple skin. The mutant showed significantly increased expression levels of photosynthesis-related proteins, stress-related proteins as well as anthocyanins biosynthesis pathway. On the other hand, substantial downregulation of mitogen-activated protein kinase 4 (MAPK4) and mevalonate kinase (MVK) were detected, indicating a promising role for the red skin color development in the mutant. Furthermore, we also hypothesize that a post-transcriptional regulation of the skin color formation occurs in the mutant through the advanced SWATH-MS analysis.ConclusionOur work provides important information on the application of proteomic methods for analysing proteomes changes in Fuji apple and highlights a clade of regulatory proteins potentially contributing for the molecular breeding of fruit skin color.Supplementary materialSupplementary information accompanies this paper at 10.1186/s12870-019-2018-1.
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