Rheumatoid arthritis

HOXA5 is a key regulator of class 3 semaphorins expression in the synovium of rheumatoid arthritis patients

Rheumatology (Oxford)Published Mechanistic study

Authors' conclusion

HOXA5 expression is reduced during the progression of RA and could be a novel therapeutic strategy for modulating the hyperplasia of the synovium, through the regulation of class 3 semaphorins expression.

Study context

Population
Synovial tissue from RA and individuals at risk (IAR) patients; Human umbilical vein endothelial cells (HUVEC) and RA fibroblast-like synoviocytes (FLS)
Comparison
RA vs individuals at risk (IAR) synovium; HOXA5, TCF-3, EBF-1 silencing in FLS and HUVEC
Outcome
Transcription factors involved in the expression of class 3 semaphorins in the synovium of RA patients
Methodological detailsin silico analysis, siRNA knockdown
  • In silico analysis
  • siRNA knockdown

Main finding

As reported in the abstract

  • mRNA expression of all class 3 semaphorins significantly lower in RA vs IAR synovium
  • In silico analysis suggested TCF-3, EBF-1 and HOXA5 as transcription factors involved in their expression
  • TCF-3, EBF-1 and HOXA5 silencing significantly reduced expression of several class 3 semaphorins in FLS and HUVEC
  • HOXA5 expression significantly reduced in RA vs IAR synovium and negatively correlated with clinical disease parameters
  • TNF-α down-regulated HOXA5 expression in FLS and HUVEC
  • HOXA5 silencing enhanced migratory and invasive capacities of FLS and viability of HUVEC

Original publication

HOXA5 is a key regulator of class 3 semaphorins expression in the synovium of rheumatoid arthritis patients. Rheumatology (Oxford). Published 18 November 2022. doi:10.1093/rheumatology/keac654

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