Anti-Inflammatory Effect of miR-197-3p-Loaded Microvesicles in Familial Mediterranean Fever Mouse Model


AKKAYA ULUM Z. Y., Nalbant E., Ulum B., AKBABA T. H., Chae J. J., Balci-Peynircioglu B.

Cell Biochemistry and Function, vol.44, no.4, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 44 Issue: 4
  • Publication Date: 2026
  • Doi Number: 10.1002/cbf.70205
  • Journal Name: Cell Biochemistry and Function
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Keywords: Familial Mediterranean Fever, inflammation, knock-in mouse model, microvesicles, miR-197-3p, potential application
  • Hacettepe University Affiliated: Yes

Abstract

Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disease triggered by Mediterranean Fever (MEFV) gene mutations that lead to spontaneous pyrin inflammasome activation and exaggerated pro-inflammatory cytokine secretion. The V726A knock-in (KI) mouse model of FMF mimics most of the clinical and immunologic manifestations of the disease, such as recurrent febrile attacks and systemic inflammation. Here, we explored the proof-of-concept evaluation of miR-197-3p-loaded microvesicles (MVs) as a therapeutic approach in the FMF KI mouse model. MVs were purified and structurally characterized through Cryo-Transmission Electron Microscopy (Cryo-TEM), establishing their integrity and size (100–1000 nm), which are compatible for nucleic acid delivery. The miR-197-3p-loaded MVs were retro-orbitally injected in FMF KI mice, and the outcomes were investigated in terms of interleukin-1beta (IL-1β) secretion, CD11b expression in total blood, spleen weight (mg) and back length as a morphological feature. miR-197-3p-loaded MV treatment in MefvV726A/V726A mouse model of FMF decreased the IL-1β level and the expression of CD11b and improved clinical inflammation manifestations. The results show that miR-197-3p-loaded MVs modulate inflammation, as well as improve phenotypic features of FMF, which is a promising, cell-free potential therapeutic strategy for autoinflammatory diseases. This study represents a preliminary proof-of-concept evaluation of miR-197-3p-loaded microvesicles in a murine FMF model, and further long-term and large-scale studies are required before clinical translation can be considered.