PMID- 38216808 OWN - NLM STAT- Publisher LR - 20240112 IS - 1559-0283 (Electronic) IS - 1085-9195 (Linking) DP - 2024 Jan 13 TI - Exosomes Derived from hucMSCs Primed with IFN-gamma Suppress the NF-kappaB Signal Pathway in LPS-Induced ALI by Modulating the miR-199b-5p/AFTPH Axis. LID - 10.1007/s12013-023-01208-2 [doi] AB - Exosomes (exos) are primarily responsible for the process of mesenchymal stem cells (MSCs) treatment for acute lung injury (ALI), but the mechanism remains unclear, particularly in altered microenvironment. Therefore, this study aimed to investigate the potential mechanism of exos derived from human umbilical cord mesenchymal stem cells (hucMSCs) primed with interferon-gamma (IFN-gamma) on ALI and to propose a promising and cell-free strategy. This study extracted exos from hucMSCs supernatant primed and unprimed with IFN-gamma marked with IFN-gamma-exos and CON-exos, which were identified and traced. IFN-gamma-exos administration to ALI models suppressed the NF-kappaB signaling pathway compared to CON-exos, which were quantified through western blot and immunohistochemical staining. Reverse transcription-quantitative polymerase chain reaction validated miR-199b-5p expression in the IFN-gamma-exos and CON-exos treatment groups. Data analysis, a dual-luciferase reporter assay, and cell transfection were conducted to investigate the target binding between miR-199b-5p and Aftiphilin (AFTPH), with AFTPH expression analyzed via cell immunofluorescence and western blot. Co-immunoprecipitation was conducted for the interaction between AFTPH and NF-kappaB p65. The result revealed that miR-199b-5p was down-regulated in the IFN-gamma-exos treatment group, which had a target binding site with AFTPH, and an interaction with NF-kappaB p65. Consequently, IFN-gamma-exos inhibited the NF-kappaB signaling pathway in ALI in vitro and in vivo through the miR-199b-5p/AFTPH axis. Our results demonstrated new directions of novel and targeted treatment for ALI. CI - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Wang, Chun AU - Wang C AD - Kunming Medical University, Kunming, Yunnan, China. AD - Department of Emergency Intensive Care Unit, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Yang, Yiran AU - Yang Y AD - Kunming Medical University, Kunming, Yunnan, China. FAU - Jiang, Chen AU - Jiang C AD - Kunming Medical University, Kunming, Yunnan, China. FAU - Xi, Cheng AU - Xi C AD - Department of Gastrointestinal Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Yin, Yunxiang AU - Yin Y AD - Department of Emergency Intensive Care Unit, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Wu, Haiying AU - Wu H AD - Department of Emergency, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. wuhaiying@kmmu.edu.cn. FAU - Qian, Chuanyun AU - Qian C AD - Department of Emergency, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. qianchuanyun@kmmu.edu.cn. LA - eng GR - 81960817/the National Natural Science Foundation of China/ GR - 82260384/the National Natural Science Foundation of China/ GR - 2020-1 - H-011/the Kunming Science and Technology Bureau/ PT - Journal Article DEP - 20240113 PL - United States TA - Cell Biochem Biophys JT - Cell biochemistry and biophysics JID - 9701934 SB - IM OTO - NOTNLM OT - AFTPH OT - Acute lung injury OT - Exosomes OT - Human umbilical cord mesenchymal stem cells OT - Interferon-gamma OT - miR-199b-5p EDAT- 2024/01/13 00:42 MHDA- 2024/01/13 00:42 CRDT- 2024/01/12 23:29 PHST- 2023/08/03 00:00 [received] PHST- 2023/11/30 00:00 [accepted] PHST- 2024/01/13 00:42 [medline] PHST- 2024/01/13 00:42 [pubmed] PHST- 2024/01/12 23:29 [entrez] AID - 10.1007/s12013-023-01208-2 [pii] AID - 10.1007/s12013-023-01208-2 [doi] PST - aheadofprint SO - Cell Biochem Biophys. 2024 Jan 13. doi: 10.1007/s12013-023-01208-2.