IFITM3 overexpression reverses insufficient healing benefits of small extracellular vesicles from high-fat-diet BMSCs in sepsis via the HMGB1 pathway
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved..
Bone marrow mesenchymal stem cells (BMSCs) are a promising new therapy for sepsis, a common cause of death in hospitals. However, the global epidemic of metabolic syndromes, including obesity and pre-obesity, threatens the health of the human BMSC pool. The therapeutic effects of BMSCs are primarily due to the secretion of the small extracellular vesicles containing lipids, proteins, and RNA. Accordingly, studies on BMSCs, their small extracellular vesicles, and their modifications in obese individuals are becoming increasingly important. In this study, we investigated the therapeutic potential of small extracellular vesicles (sEVs) from high-fat diet BMSCs (sEVsHFD) in sepsis-induced liver-heart axis injury. We found that sEVsHFD yielded diminished therapeutic benefits compared to sEVs from chow diet BMSCs (sEVsCD). We subsequently verified that IFITM3 significantly differed in sEVsCD and sEVsHFD, alternating in septic liver tissue, and indicating its potential as a remodeling target of sEVs. IFITM3-overexpressed high-fat-diet BMSCs (HFD-BMSCs) showed that corresponding sEVs (sEVsHFD-IFITM3) markedly ameliorated liver-heart axis injury during sepsis. Lastly, we identified the protective action mechanisms of sEVsHFD-IFITM3 in sepsis-induced organ failure and HMGB1 expression and secretion was altered in septic liver and serum while HMGB1 has been demonstrated as a critical mediator of multi-organ failure in sepsis. These findings indicate that IFITM3 overexpression regenerates the therapeutic benefit of sEVs from HFD-BMSCs in sepsis via the HMGB1 pathway.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:126 |
|---|---|
| Enthalten in: |
International immunopharmacology - 126(2024) vom: 05. Jan., Seite 111250 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cui, Jun [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Bone marrow stem cells |
|---|
| Anmerkungen: |
Date Completed 12.01.2024 Date Revised 03.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.intimp.2023.111250 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM364979690 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM364979690 | ||
| 003 | DE-627 | ||
| 005 | 20240404234418.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.intimp.2023.111250 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1364.xml |
| 035 | |a (DE-627)NLM364979690 | ||
| 035 | |a (NLM)38006752 | ||
| 035 | |a (PII)S1567-5769(23)01577-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cui, Jun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a IFITM3 overexpression reverses insufficient healing benefits of small extracellular vesicles from high-fat-diet BMSCs in sepsis via the HMGB1 pathway |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.01.2024 | ||
| 500 | |a Date Revised 03.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Bone marrow mesenchymal stem cells (BMSCs) are a promising new therapy for sepsis, a common cause of death in hospitals. However, the global epidemic of metabolic syndromes, including obesity and pre-obesity, threatens the health of the human BMSC pool. The therapeutic effects of BMSCs are primarily due to the secretion of the small extracellular vesicles containing lipids, proteins, and RNA. Accordingly, studies on BMSCs, their small extracellular vesicles, and their modifications in obese individuals are becoming increasingly important. In this study, we investigated the therapeutic potential of small extracellular vesicles (sEVs) from high-fat diet BMSCs (sEVsHFD) in sepsis-induced liver-heart axis injury. We found that sEVsHFD yielded diminished therapeutic benefits compared to sEVs from chow diet BMSCs (sEVsCD). We subsequently verified that IFITM3 significantly differed in sEVsCD and sEVsHFD, alternating in septic liver tissue, and indicating its potential as a remodeling target of sEVs. IFITM3-overexpressed high-fat-diet BMSCs (HFD-BMSCs) showed that corresponding sEVs (sEVsHFD-IFITM3) markedly ameliorated liver-heart axis injury during sepsis. Lastly, we identified the protective action mechanisms of sEVsHFD-IFITM3 in sepsis-induced organ failure and HMGB1 expression and secretion was altered in septic liver and serum while HMGB1 has been demonstrated as a critical mediator of multi-organ failure in sepsis. These findings indicate that IFITM3 overexpression regenerates the therapeutic benefit of sEVs from HFD-BMSCs in sepsis via the HMGB1 pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bone marrow stem cells | |
| 650 | 4 | |a IFITM3 | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Sepsis | |
| 650 | 4 | |a Small extracellular vesicles | |
| 650 | 7 | |a fragilis protein, mouse |2 NLM | |
| 650 | 7 | |a HMGB1 Protein |2 NLM | |
| 650 | 7 | |a HMGB1 protein, mouse |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 700 | 1 | |a Chen, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Shan, Wenju |e verfasserin |4 aut | |
| 700 | 1 | |a Jian, Yuhong |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Linqi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Panpan |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Wei |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International immunopharmacology |d 2001 |g 126(2024) vom: 05. Jan., Seite 111250 |w (DE-627)NLM112639542 |x 1878-1705 |7 nnns |
| 773 | 1 | 8 | |g volume:126 |g year:2024 |g day:05 |g month:01 |g pages:111250 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.intimp.2023.111250 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 126 |j 2024 |b 05 |c 01 |h 111250 | ||