bims-evecad 2026-01-25 papers

Issue of 2026–01–25
two papers selected by
Cliff Dominy

Mol Cell Proteomics. 2026 Jan 19. pii: S1535-9476(26)00006-X. [Epub ahead of print] 101511

Infosomes as Inflammatory Mediators: Proteomic Profiling of Proteins Enriched in Inflammatory Extracellular Vesicles.

Semin Lee, Minjun Kim, Seungmin Lee, Hyo-Jin Kim, Ki-Jun Ryu, Sang-Hun Kim, Hong-Yeoul Ryu, Kyunghee Lee, Kwang Dong Kim, Jiyun Yoo, Cheol Hwangbo, Yong-Ho Choe, Seongchan Kim, Seung Pil Yun, Hyuk-Kwon Kwon.

Extracellular vesicles (EVs), including exosomes and microvesicles, act as transmitters of various biological signals through cell-cell communication. Although EVs derived from immune response cells have been partially studied, the characteristics of EVs mediated by NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation remain unclear. Here, we characterize inflammatory EVs, termed infosomes, derived from NLRP3 inflammasome-activated macrophages, which play a role in inducing inflammation. Proteomic analysis revealed that EVs production was increased in macrophages with activated NLRP3 inflammasomes and that these EVs were enriched with marker proteins involved in metabolism, membrane structure, and cytoskeletal organization. Furthermore, significantly increased proteins were associated with signaling pathways and biological processes related to immune response, phagocytosis, endocytosis, and neurodegenerative diseases. Crucially, these alterations in EV secretion and molecular composition were dependent on NLRP3 and its subsequent inflammasome activity. Functionally, these infosomes were shown to amplify the expression of inflammatory factors in both macrophages and endothelial cells (HUVECs). These findings provide insights into the biological roles of infosomes, suggesting that EVs generated and loaded by NLRP3 inflammasome activation act as key biological mediators that disseminate and amplify inflammatory responses through cell-cell communication. This highlights their potential as novel biomarkers and therapeutic targets for inflammatory diseases.

Keywords: Extracellular vesicles; Inflammation; Infosomes; NLRP3 Inflammasome; Proteomics

DOI: https://doi.org/10.1016/j.mcpro.2026.101511

Bioeng Transl Med. 2026 Jan;11(1): e70046

Hypoxia-preconditioned MiotEVs from bone marrow mesenchymal stem cells inhibit myocardial infarction-induced cardiac fibrosis.

Jungang Nie, Hongwen Zhu, Zhiming Gao, Liang Wang.

Hypoxia-preconditioned bone marrow mesenchymal stem cell-derived mitochondrial extracellular vesicles (Hypoxia-BMSC MitoEVs) emerged as a novel therapeutic candidate for myocardial infarction (MI)-induced cardiac fibrosis. Here, we demonstrate that MitoEVs isolated from hypoxic BMSCs, rich in intact mitochondria and the RNA-binding protein Quaking (QKI), potently inhibited TGF-β1-driven myofibroblast activation in vitro by suppressing α-SMA and collagen expression while restoring mitochondrial oxidative phosphorylation and metabolic balance. In a murine MI model, systemic delivery of Hypoxia-BMSC MitoEVs attenuated cardiac fibrosis, reduced infarct size, and improved left ventricular function. Pharmacological inhibition of mitochondrial ATP synthase in MitoEVs similarly diminished their therapeutic efficacy. Mechanistically, MitoEVs delivered QKI protein to cardiac fibroblasts, where it inhibited translation of fibrotic mRNAs via m7G-modified RNA interactions. Genetic ablation of QKI in BMSCs abrogated MitoEV-mediated antifibrotic effects both in vitro and in vivo, confirming QKI as a critical effector. These results suggested that both QKI-driven translational suppression and mitochondrial bioenergetics underpin their antifibrotic action. These findings highlight Hypoxia-BMSC MitoEVs as a therapeutic strategy to mitigate post-MI fibrosis, warranting further exploration for clinical translation.

Keywords: MitoEVs; cardiac fibrosis; energy metabolism, glycolysis, QKI; myocardial infarction

DOI: https://doi.org/10.1002/btm2.70046