MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis.

Area of Science:

• Immunology
• Epigenetics
• Molecular Biology

Background:

• Jumonji Domain-Containing Protein 3 (JMJD3)/lysine demethylase 6B (KDM6B) is an epigenetic regulator.
• KDM6B mRNA is elevated in ANCA-associated vasculitis (AAV) leukocytes, potentially increasing proteinase 3 (PR3) mRNA expression.
• MicroRNA-941 (miR-941) targets KDM6B mRNA, inhibiting JMJD3 production.

Purpose of the Study:

• To investigate if reduced miR-941 expression in polymorphonuclear granulocytes (PMNs) from granulomatosis with polyangiitis (GPA) patients contributes to higher JMJD3 levels.
• To determine if miR-941 regulates KDM6B mRNA levels in PMNs.

Main Methods:

• Compared CD16 and FCGR3B expression in PMNs from GPA patients (n=8) and healthy controls (n=11).
• Quantified PRTN3, KDM6B mRNA, and miR-941 expression in PMNs.
• Transfected PLB-985 cells with pre-miR-941 to assess KDM6B mRNA regulation.

Main Results:

• No significant difference in PMN maturation markers between GPA patients and controls.
• PRTN3 mRNA, KDM6B mRNA, and miR-941 expression levels were comparable in GPA patients and healthy controls.
• Transfection of pre-miR-941 did not consistently reduce KDM6B mRNA levels in PLB-985 cells.

Conclusions:

• Decreased miR-941 expression in PMNs is not a pathogenic mechanism in GPA.
• miR-941 does not uniformly regulate KDM6B mRNA levels via transcript degradation in neutrophils.
• The proposed pathway involving miR-941, KDM6B, and PRTN3 is unlikely to be involved in GPA pathogenesis.