Unveiling the Cutting-Edge Impact of Polarized Macrophage-Derived Extracellular Vesicles and MiRNA Signatures on TGF-β Regulation within Lung Fibroblasts

Alvise Casara; Maria Conti; Nicol Bernardinello; Mariaenrica Tinè; Simonetta Baraldo; Graziella Turato; Umberto Semenzato; Alessandro Celi; Paolo Spagnolo; Marina Saetta; Manuel G. Cosio; Tommaso Neri; Davide Biondini; Erica Bazzan

doi:10.3390/ijms25137490

International Journal of Molecular Sciences (Jul 2024)

Unveiling the Cutting-Edge Impact of Polarized Macrophage-Derived Extracellular Vesicles and MiRNA Signatures on TGF-β Regulation within Lung Fibroblasts

Alvise Casara,
Maria Conti,
Nicol Bernardinello,
Mariaenrica Tinè,
Simonetta Baraldo,
Graziella Turato,
Umberto Semenzato,
Alessandro Celi,
Paolo Spagnolo,
Marina Saetta,
Manuel G. Cosio,
Tommaso Neri,
Davide Biondini,
Erica Bazzan

Affiliations

Alvise Casara: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Maria Conti: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Nicol Bernardinello: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Mariaenrica Tinè: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Simonetta Baraldo: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Graziella Turato: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Umberto Semenzato: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Alessandro Celi: Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, Università degli Studi di Pisa, 56124 Pisa, Italy
Paolo Spagnolo: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Marina Saetta: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Manuel G. Cosio: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Tommaso Neri: Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, Università degli Studi di Pisa, 56124 Pisa, Italy
Davide Biondini: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy
Erica Bazzan: Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy

DOI: https://doi.org/10.3390/ijms25137490
Journal volume & issue: Vol. 25, no. 13
p. 7490

Abstract

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Depending on local cues, macrophages can polarize into classically activated (M1) or alternatively activated (M2) phenotypes. This study investigates the impact of polarized macrophage-derived Extracellular Vesicles (EVs) (M1 and M2) and their cargo of miRNA-19a-3p and miRNA-425-5p on TGF-β production in lung fibroblasts. EVs were isolated from supernatants of M0, M1, and M2 macrophages and quantified using nanoscale flow cytometry prior to fibroblast stimulation. The concentration of TGF-β in fibroblast supernatants was measured using ELISA assays. The expression levels of miRNA-19a-3p and miRNA-425-5p were assessed via TaqMan-qPCR. TGF-β production after stimulation with M0-derived EVs and with M1-derived EVs increased significantly compared to untreated fibroblasts. miRNA-425-5p, but not miRNA-19a-3p, was significantly upregulated in M2-derived EVs compared to M0- and M1-derived EVs. This study demonstrates that EVs derived from both M0 and M1 polarized macrophages induce the production of TGF-β in fibroblasts, with potential regulation by miRNA-425-5p.

Published in International Journal of Molecular Sciences

ISSN: 1661-6596 (Print); 1422-0067 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General); Science: Chemistry
Website: http://www.mdpi.com/journal/ijms

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