Proinflammatory S100A9 Regulates Differentiation and Aggregation of Neural Stem Cells

Abstract

Inflammation is the primary pathological feature of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease. Proinflammatory molecules (e.g., S100A9) play important roles during the progression of the diseases by regulating behavior and fate of multiple cell types in the nervous system. Our earlier studies reveal that S100A9 is toxic to neurons, and its interaction with Aβ peptides leads to the formation of large nontoxic amyloidogenic aggregates, suggesting a protective role of coaggregation with Aβ amyloids. We herein demonstrate that S100A9 interacts with neural stem cells (NSCs) and causes NSC differentiation. In the brain of transgenic AD mouse models, we found large quantities of proinflammatory S100A9, which colocalizes with the differentiated NSCs. NSC sphere formation, which is a representative character of NSC stemness, is also substantially inhibited by S100A9. These results suggest that S100A9 is a representative marker for the inflammatory conditions in AD, and it promotes NSC differentiation. Intriguingly, in contrast to the death of both stem and differentiated NSCs caused by high S100A9 doses, S100A9 at a moderate concentration is toxic only to the early differentiated NSCs but not the stem cells. We therefore postulate that, at the early stage of AD, the expression of S100A9 leads to NSC differentiation, which remedies the neuron damage. The application of drugs, which help maintain NSC stemness (e.g., the platelet-derived growth factor, PDGF), may help overcome the acute inflammatory conditions and improve the efficacy of NSC transplantation therapy.

Three Potential Tumor Markers Promote Metastasis and Recurrence of Colorectal Cancer by Regulating the Inflammatory Response: ADAM8, LYN, and S100A9

“…Zhao et al reported that downregulation of S100A9 mitigated lipopolysaccharide-induced inflammation in vitro [ 42 ]. Previous studies have suggested that S100A9 is a representative marker of the inflammatory state in Alzheimer's disease and promotes the differentiation of neural stem cells [ 43 ]. Using short hairpin RNA to inhibit S100A9 in cancer cells significantly reduced the cells' migration and invasion in culture, suggesting that S100A9 has a critical role in the invasiveness of tumor cells [ 44 ].…”

Joint analysis of the metabolomics and transcriptomics uncovers the dysregulated network and develops the diagnostic model of high-risk neuroblastoma

“…In addition, a close association between these 3 genes and NB was also found. Overexpression of S100A9 enhanced the proliferation, migration and invasion of NB cells 54 – 57 , suggesting that S100A9 may be involved in the development of NB tumors 58 . In this study, S100A9 increased 7.23-fold in RNA-seq, therefore the high expression of S100A9 may be related to the risk classification of NB.…”

Identification S100A9 as a potential biomarker in neuroblastoma

“…Characterized by calcium-binding EF hand motifs, S100 family comprise of more than 20 homologous proteins. Studies have revealed that S100A9 induced activation of NF-kB which participate in a broad range of intracellular and extracellular functions by regulating angiogenesis, tumor migration, wound healing, cell apoptosis, proliferation, differentiation, and inflammation [9,[37][38][39][40][41][42]. In addition, it has become increasingly evident that S100A9 acts as a potent amplifier of inflammation in tumor.…”