PMID- 37790380
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
DP  - 2023 Sep 12
TI  - Proteomic analysis of signaling pathways modulated by FABP5 in macrophages.
LID - rs.3.rs-3332029 [pii]
LID - 10.21203/rs.3.rs-3332029/v1 [doi]
AB  - BACKGROUND: While acute inflammation serves essential functions in maintaining 
      tissue homeostasis, chronic inflammation is causally linked to many diseases. 
      Macrophages are a major cell-type that orchestrates inflammatory processes. 
      During inflammation, macrophages undergo polarization and activation, thereby 
      mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that 
      regulate ensuing macrophage functions. Fatty acid binding protein 5 (FABP5) is a 
      lipid chaperone that is highly expressed in macrophages. FABP5 deletion is 
      implicated in driving macrophages towards an anti-inflammatory phenotype, yet the 
      signaling pathways regulated by macrophage FABP5 have not been systematically 
      profiled. Herein, we leveraged proteomic and phosphoproteomic approaches to 
      characterize pathways modulated by FABP5 in M1 and M2 polarized bone marrow 
      derived macrophages (BMDMs). RESULTS: Stable isotope labeling by amino acids 
      (SILAC) based analysis of M1 and M2 polarized wild-type (WT) and FABP5 knockout 
      (KO) BMDMs revealed numerous differentially regulated proteins and 
      phosphoproteins. FABP5 deletion impacted several downstream pathways associated 
      with inflammation, cytokine production, oxidative stress, and kinase activity. 
      Kinase enrichment analysis based on phosphorylated sites revealed key kinases, 
      including members of the GRK family, that were altered in FABP5 KO BMDMs. 
      Reactive oxygen species (ROS) levels were elevated in M1 polarized KO 
      macrophages, consistent with the differential protein expression profiles. 
      CONCLUSIONS: This study represents a comprehensive characterization of the impact 
      of FABP5 deletion upon the proteomic and phosphoproteomic landscape of M1 and M2 
      polarized BMDMs. Loss of FABP5 altered multiple pathways implicated in 
      inflammatory responses and macrophage function. This work provides a foundation 
      for future studies seeking to investigate the therapeutic potential of FABP5 
      inhibition in pathophysiological states resulting from dysregulated inflammatory 
      signaling.
FAU - Doswell, Faniya
AU  - Doswell F
AD  - Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, NY, 
      USA.
AD  - Department of Anesthesiology, Renaissance School of Medicine, Stony Brook 
      University, Stony Brook, NY, USA.
FAU - Haley, John D
AU  - Haley JD
AD  - Department of Pathology, Renaissance School of Medicine, Stony Brook University, 
      Stony Brook, NY, USA.
AD  - Stony Brook Biological Mass Spectrometry Facility, Renaissance School of 
      Medicine, Stony Brook University, Stony Brook, USA.
FAU - Kaczocha, Martin
AU  - Kaczocha M
AD  - Department of Anesthesiology, Renaissance School of Medicine, Stony Brook 
      University, Stony Brook, NY, USA.
LA  - eng
GR  - R01 DA035949/DA/NIDA NIH HHS/United States
PT  - Preprint
DEP - 20230912
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
PMC - PMC10543284
OTO - NOTNLM
OT  - FABP5
OT  - Inflammation
OT  - fatty acid binding protein 5
OT  - macrophage
OT  - phosphoproteomics
OT  - polarization
OT  - proteomics
COIS- Competing interest The authors declare no competing interests.
EDAT- 2023/10/04 06:43
MHDA- 2023/10/04 06:44
PMCR- 2023/10/02
CRDT- 2023/10/04 04:03
PHST- 2023/10/04 06:44 [medline]
PHST- 2023/10/04 06:43 [pubmed]
PHST- 2023/10/04 04:03 [entrez]
PHST- 2023/10/02 00:00 [pmc-release]
AID - rs.3.rs-3332029 [pii]
AID - 10.21203/rs.3.rs-3332029/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2023 Sep 12:rs.3.rs-3332029. doi: 10.21203/rs.3.rs-3332029/v1.