Reconstruction of the Cytokine Signaling in Lysosomal Storage Diseases by Literature Mining and Network Analysis
Autor: | Enrico Domenici, Alan Ramponi, Danilo Tomasoni, Silvia Parolo, Susana Neves-Zaph, Karim Azer, Rosario Lombardo, Pranami Bora, Chanchala D. Kaddi |
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Rok vydání: | 2021 |
Předmět: |
QH301-705.5
Systems biology medicine.medical_treatment Inflammation Context (language use) Biology Cell and Developmental Biology cytokine medicine Biology (General) natural language processing lysosomal storage diseases Transcription factor Original Research ASMD text-mining systems biology Cell Biology medicine.disease Fabry disease Sphingolipid Cell biology Cytokine Fabry Gaucher Acid sphingomyelinase medicine.symptom Developmental Biology medicine.drug |
Zdroj: | Frontiers in Cell and Developmental Biology Frontiers in Cell and Developmental Biology, Vol 9 (2021) |
ISSN: | 2296-634X |
Popis: | Lysosomal storage diseases (LSDs) are characterized by the abnormal accumulation of substrates in tissues due to the deficiency of lysosomal proteins. Among the numerous clinical manifestations, chronic inflammation has been consistently reported for several LSDs. However, the molecular mechanisms involved in the inflammatory response are still not completely understood. In this study, we performed text-mining and systems biology analyses to investigate the inflammatory signals in three LSDs characterized by sphingolipid accumulation: Gaucher disease, Acid Sphingomyelinase Deficiency (ASMD), and Fabry Disease. We first identified the cytokines linked to the LSDs, and then built on the extracted knowledge to investigate the inflammatory signals. We found numerous transcription factors that are putative regulators of cytokine expression in a cell-specific context, such as the signaling axes controlled by STAT2, JUN, and NR4A2 as candidate regulators of the monocyte Gaucher disease cytokine network. Overall, our results suggest the presence of a complex inflammatory signaling in LSDs involving many cellular and molecular players that could be further investigated as putative targets of anti-inflammatory therapies. |
Databáze: | OpenAIRE |
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