Senescent Macrophages Release Inflammatory Cytokines and RNA-Loaded Extracellular Vesicles to Circumvent Fibroblast Senescence

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2024 May 25

PMID 38791051

Authors

Camille Laliberte

Bianca Bosse

Veronique Bourdeau

Luis I Prieto

Geneve Perron-Deshaies

Nhung Vuong-Robillard

Sebastian Igelmann

Lisbeth Carolina Aguilar

Marlene Oeffinger

Darren J Baker

Luc DesGroseillers

Gerardo Ferbeyre

Affiliations

Soon will be listed here.

Abstract

Senescent cells, which accumulate with age, exhibit a pro-inflammatory senescence-associated secretory phenotype (SASP) that includes the secretion of cytokines, lipids, and extracellular vesicles (EVs). Here, we established an in vitro model of senescence induced by Raf-1 oncogene in RAW 264.7 murine macrophages (MΦ) and compared them to senescent MΦ found in mouse lung tumors or primary macrophages treated with hydrogen peroxide. The transcriptomic analysis of senescent MΦ revealed an important inflammatory signature regulated by NFkB. We observed an increased secretion of EVs in senescent MΦ, and these EVs presented an enrichment for ribosomal proteins, major vault protein, pro-inflammatory miRNAs, including miR-21a, miR-155, and miR-132, and several mRNAs. The secretion of senescent MΦ allowed senescent murine embryonic fibroblasts to restart cell proliferation. This antisenescence function of the macrophage secretome may explain their pro-tumorigenic activity and suggest that senolytic treatment to eliminate senescent MΦ could potentially prevent these deleterious effects.

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