PXD045426

PXD045426 is an original dataset announced via ProteomeXchange.

Title	Global proteomics insights for a novel small compound targeting the non-integrin Laminin Receptor in a macrophage cell model
Description	Monocytes and macrophages are the first barrier of the innate immune system, which interact with agents causing osteoarthritis or other conditions, leading to the release of proinflammatory mediators that exacerbate inflammation. The aim of this study was to investigate the proteomic changes in THP-1 monocytes differentiated to macrophages, pre- or -post small compound treatments and in the presence or absence of a proinflammatory stimulus, Lipopolysaccharide (LPS). This study aimed to discover and isolate small compounds that mimic the interaction between Pigment derived growth factor (PEDF) and its 37/67kDa Laminin receptor (LR) with potential anti-inflammatory activity. Our results suggested that novel compounds targeting the LR-PEDF interface can be useful for modulating anti-inflammatory effects. Several compounds were selected based on in silico docking at the PEDF/LR interface and examined for their ability to reduce IL1B expression in a macrophage cell model. Compound C3 showed the highest efficacy in reducing IL1B expression in the presence of LPS proinflammatory stimulus. Proteomics analysis revealed that C3 treatment altered the global proteomic profile of THP-1 activated macrophages, affecting pathways such as MYC targets, oxidative phosphorylation, and mTORC1 signaling. The analysis also highlighted the involvement of key regulators, including RPSA and MYC, and their interactions with other proteins such as ribosome proteins and cell cycle regulators. Furthermore, the downregulated proteome analysis revealed shared and unique pathways affected by the treatments, including processes related to actin cytoskeleton, translation, and inflammatory response. Protein-protein interaction networks suggested the potential involvement of transcription factors like MYC and the interconnectedness of signaling pathways in mediating the effects of the treatments. Overall, these findings provide valuable insights into the potential anti-inflammatory activity and underlying mechanisms of compound C3, emphasizing its relevance for further investigation in the context of inflammatory conditions.
HostingRepository	MassIVE
AnnounceDate	2023-12-14
AnnouncementXML	Submission_2023-12-14_10:36:38.042.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tiago Sobreira
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-17 16:54:32	ID requested
⏵ 1	2023-12-14 10:36:38	announced

no publication

submitter keyword: small molecules, PEDF, non-integrin laminin receptor, RPSA, drug discovery, anti-inflammatory, macrophages

Marxa L Figueiredo
contact affiliation	Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue
contact email	mlfiguei@purdue.edu
lab head
Tiago Sobreira
contact affiliation	Covant Therapeutics
contact email	tiagosobreira@yahoo.com.br
dataset submitter

MassIVE dataset URI

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