PMID- 36570020 OWN - NLM STAT- MEDLINE DCOM- 20221227 LR - 20221230 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2022 DP - 2022 TI - MiR-181a-5p Delivered by Adipose-Derived Mesenchymal Stem Cell Exosomes Alleviates Klebsiella pneumonia Infection-Induced Lung Injury by Targeting STAT3 Signaling. PG - 5188895 LID - 10.1155/2022/5188895 [doi] LID - 5188895 AB - BACKGROUND: Klebsiella pneumoniae (K. pneu) is a leading cause of gram-negative pneumonia, which requires effective treatment. Adipose-derived mesenchymal stem cell- (ADSC-) derived exosomal microRNAs (miRNAs) have presented the inhibitory effect of multiple diseases. However, the function of ADSC-derived exosomal miRNAs in K. pneu remains unclear. AIM: In this study, we aimed to explore the effect of ADSC-derived exosomal miR-181-5p on K. pneu infection-induced lung injury. METHODS: C57BL/6 mouse model was established by infection of K. pneu. ADSCs and exosomes were extracted and characterized in vitro. The translocation of ADSC-derived exosomes to bone marrow-derived macrophages (BMDMs) was detected. The level of miR-181a-5p was detected by real-time PCR. The secretion of inflammatory factors was determined by ELISA. The interaction between miR-181a-5p with STAT3 was identified. RESULTS: We successfully isolated the ADSCs that express positive markers CD90 and CD105 rather than CD31 and CD45. The exosomal miR-181a-5p secreted by ADSCs were internalized by BMDM and K. pneu infection stimulated the miR-181a-5p level in bronchoalveolar lavage fluid (BALF) and BMDM. ADSC-derived exosomal miR-181a-5p repressed pulmonary outgrowth and dissemination of K. pneu infection in mice, repressed cellular infiltration in lung tissue, and attenuated the inflammasome activity and the levels of IL-1beta and IL-18 in the lung. Mechanically, miR-181a-5p was able to inhibit STAT3 expression at posttranscriptional levels and repressed Nlrp3 and Asc expression in BMDM. CONCLUSION: Consequently, we concluded that ADSC-derived exosomal miR-181a-5p alleviated Klebsiella pneumonia infection-induced lung injury by targeting STAT3 signaling. ADSC-derived exosomal miR-181a-5p may serve as a potential candidate for the treatment of Klebsiella pneumonia infection-induced lung injury. CI - Copyright (c) 2022 Ren-Jing Hu et al. FAU - Hu, Ren-Jing AU - Hu RJ AD - Department of Laboratory Medicine, Wuxi Second People's Hospital Affiliated to Nanjing Medical University, Wuxi City, 214000 Jiangsu Province, China. FAU - Chen, Xiao-Chun AU - Chen XC AD - Department of Laboratory Medicine, Taizhou Second People's Hospital, Taizhou City, 225411 Jiangsu Province, China. FAU - Xu, Lei AU - Xu L AD - Department of Oral and Maxillofacial Surgery, Wuxi Stomatological Hospital, Wuxi City, 214001 Jiangsu Province, China. FAU - Rui, Xiao-Hong AU - Rui XH AD - Department of Laboratory Medicine, Wuxi Fifth People's Hospital, Wuxi City, 214000 Jiangsu Province, China. FAU - Wan, Lin AU - Wan L AD - Department of Laboratory Medicine, Wuxi Second People's Hospital Affiliated to Nanjing Medical University, Wuxi City, 214000 Jiangsu Province, China. FAU - Lu, Jie AU - Lu J AD - Department of Laboratory Medicine, Wuxi Second People's Hospital Affiliated to Nanjing Medical University, Wuxi City, 214000 Jiangsu Province, China. FAU - Liu, Jun AU - Liu J AD - Department of Laboratory Medicine, Wuxi Fifth People's Hospital, Wuxi City, 214000 Jiangsu Province, China. FAU - Pei, Hao AU - Pei H AUID- ORCID: 0000-0002-2422-8419 AD - Department of Laboratory Medicine, Wuxi Fifth People's Hospital, Wuxi City, 214000 Jiangsu Province, China. LA - eng PT - Journal Article DEP - 20221214 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (MicroRNAs) SB - IM MH - Mice MH - Animals MH - Klebsiella pneumoniae/metabolism MH - *Exosomes/metabolism MH - *Lung Injury/metabolism MH - Mice, Inbred C57BL MH - *MicroRNAs/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - *Pneumonia/metabolism PMC - PMC9771653 COIS- The authors declare that they have no conflicts of interest. EDAT- 2022/12/27 06:00 MHDA- 2022/12/28 06:00 PMCR- 2022/12/14 CRDT- 2022/12/26 04:27 PHST- 2021/06/18 00:00 [received] PHST- 2022/01/16 00:00 [revised] PHST- 2022/01/27 00:00 [accepted] PHST- 2022/12/26 04:27 [entrez] PHST- 2022/12/27 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] PHST- 2022/12/14 00:00 [pmc-release] AID - 10.1155/2022/5188895 [doi] PST - epublish SO - Mediators Inflamm. 2022 Dec 14;2022:5188895. doi: 10.1155/2022/5188895. eCollection 2022.