Anti-fibrotic effect of Spirulina maxima-derived extracellular vesicles: possible role of PARK7 and HSP70 chaperones

Szebeni, Beáta and Bernáth, Mária and Bokrossy, Péter and Pap, Domonkos and Molnár, Zoltán and Mészáros, Tamás and Lenzinger, Dorina and Visnovitz, Tamás and Pálmai, Marcell and Mihály, Judith and Varga, Zoltán and Fekete, Nóra and Pállinger, Éva and Veres-Székely, Apor and Szász, Csenge and Buzás, Edit and Szabó, Attila J. and Vannay, Ádám (2026) Anti-fibrotic effect of Spirulina maxima-derived extracellular vesicles: possible role of PARK7 and HSP70 chaperones. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, 14. ISSN 2296-4185

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Abstract

Introduction: Spirulina maxima (Sm), a blue-green microalgae, is well known for its rich nutritional composition, antioxidant, and anti-inflammatory properties. In this study, we found that small extracellular vesicles (sEVs) isolated from Sm exhibit antifibrotic activity.Methods: Sm derived sEVs (Sm_sEV) were purified from the Sm culture medium using tangential flow filtration (TFF), followed by size-exclusion chromatography (SEC). Characterization of the sEVs was performed using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), immunogold TEM, surface-enhanced IR spectroscopy (SEIRS), and flow cytometry (FC). Internalization of DiI-labeled sEVs by human primary peritoneal mesothelial cells (P-MCs) and peritoneal fibroblasts (p-FBs) was examined using fluorescence microscopy. The effect of sEVs on mesenchymal transition of P-MCs and activation of P-FBs was investigated by immunofluorescent staining, MTT cell-proliferation, and Sirius Red collagen accumulation assays, respectively. The antifibrotic relevance of Sm_sEV was further investigated in a chlorhexidine digluconate (CG)-induced mouse model of peritoneal fibrosis.Results: The isolated Sm_sEV exhibited a spherical morphology, with a size range of 150.0 ± 67.6 nm, and the protein-to-lipid ratio (P/L_spectr) was 2.27 ± 0.07. The sEVs cargo contained Parkinson’s disease protein 7 (PARK7), and heat shock protein 70 (HSP70). DiI-labeled sEVs were successfully internalized by both P-MCs and P-FBs and inhibited TGF-β-induced mesenchymal transition in P-MCs and the collagen production and PDGF-B-induced proliferation in P-FBs. In vivo, intraperitoneal administration of Sm_sEVs reduced CG-induced submesothelial thickening, fibronectin, and collagen type I alpha 1 immunopositivity, and increased cytokeratin 18, immunopositivity in the mesothelial layer.Discussion: These findings highlight the antifibrotic effect of Sm_sEV and support their further investigation in the context of fibrosis.

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