Unveiling the Nexus: Cellular Metabolomics Unravels the Impact of Estrogen on Nicotinamide Metabolism in Mitigating Rheumatoid Arthritis Pathogenesis.
Swati MalikDebolina ChakrabortyPrachi AgnihotriVijay KumarSagarika BiswasPublished in: Metabolites (2024)
Rheumatoid arthritis (RA) is a metabolic joint disorder influenced by hormonal regulation, notably estrogen, which plays a cytoprotective role against inflammation. While estrogen's impact on RA pathogenesis has been studied, the altered metabolite expression under estrogen's influence remains unexplored. This study investigated the changes in the metabolome of synovial fibroblasts isolated from RA patients under 17β-estradiol (E2) using the liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach followed by multivariate and biological pathway analysis along with in vitro validation. Results identified 3624 m / z , among which eight metabolites were significant ( p < 0.05). Nicotinate and nicotinamide metabolism was found to be highly correlated with the treatment of E2, with metabolites NAD + and 1-methynicotinamide (1-MNA) upregulated by E2 induction in RA-FLS. PharmMapper analysis identified potential gene targets of 1-MNA, which were further matched with RA gene targets, and thus, STAT1, MAPK14, MMP3, and MMP9 were concluded to be the common targets. E2 treatment affected the expression of these gene targets and ameliorated the development of oxidative stress associated with RA inflammation, which can be attributed to increased concentration of 1-MNA. Thus, an LC-MS/MS-based metabolomics study revealed the prominent role of estrogen in preventing inflammatory progression in RA by altering metabolite concentration, which can support its therapeutic capacity in remitting RA.
Keyphrases
- rheumatoid arthritis
- disease activity
- oxidative stress
- ankylosing spondylitis
- estrogen receptor
- tandem mass spectrometry
- liquid chromatography
- mass spectrometry
- interstitial lung disease
- systemic lupus erythematosus
- poor prognosis
- copy number
- multiple sclerosis
- ultra high performance liquid chromatography
- genome wide
- ms ms
- simultaneous determination
- dna damage
- high performance liquid chromatography
- end stage renal disease
- cell proliferation
- newly diagnosed
- gas chromatography
- dna methylation
- ischemia reperfusion injury
- diabetic rats
- risk assessment
- long non coding rna
- skeletal muscle
- binding protein
- peritoneal dialysis
- ejection fraction
- idiopathic pulmonary fibrosis
- gene expression
- insulin resistance
- climate change
- transcription factor
- combination therapy
- heat stress
- patient reported
- heat shock protein