MALAT1 shuttled by extracellular vesicles promotes M1 polarization of macrophages to induce acute pancreatitis via miR‐181a‐5p/HMGB1 axis
| العنوان: | MALAT1 shuttled by extracellular vesicles promotes M1 polarization of macrophages to induce acute pancreatitis via miR‐181a‐5p/HMGB1 axis |
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| المؤلفون: | Jie Liu, Rui Zhang, Longfei Pan, Zhong Liu, Zhuo Peng, Honghong Pei, Zequn Niu, Yanxia Gao, Liming Wang |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Apoptosis, Mice, Databases, Genetic, HMGB1 Protein, MALAT1, biology, Chemistry, NF-kappa B, Middle Aged, Long non-coding RNA, Hedgehog signaling pathway, Cell biology, long non‐coding RNA, metastasis‐associated lung adenocarcinoma transcript‐1, Molecular Medicine, Female, RNA, Long Noncoding, Original Article, Disease Susceptibility, Signal Transduction, Adult, acute pancreatitis, HMGB1, M1 polarization of macrophages, Extracellular Vesicles, Downregulation and upregulation, In vivo, Cell Line, Tumor, medicine, Animals, Humans, Gene Silencing, high‐mobility group box 1 protein, Aged, Gene Expression Profiling, Macrophages, Original Articles, Cell Biology, Macrophage Activation, medicine.disease, Toll-Like Receptor 4, Disease Models, Animal, MicroRNAs, Gene Expression Regulation, Pancreatitis, microRNA‐181a‐5p, TLR4, biology.protein |
| الوصف: | Acute pancreatitis (AP) is a serious condition carrying a mortality of 25–40%. Extracellular vesicles (EVs) have reported to exert potential functions in cell‐to‐cell communication in diseases such as pancreatitis. Thus, we aimed at investigating the mechanisms by which EV‐encapsulated metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) might mediate the M1 polarization of macrophages in AP. Expression patterns of MALAT1, microRNA‐181a‐5p (miR‐181a‐5p) and high‐mobility group box 1 protein (HMGB1) in serum of AP patients were determined. EVs were isolated from serum and pancreatic cells. The binding affinity among miR‐181a‐5p, MALAT1 and HMGB1 was identified. AP cells were co‐cultured with EVs from caerulein‐treated MPC‐83 cells to determine the levels of M1/2 polarization markers and TLR4, NF‐κB and IKBa. Finally, AP mouse models were established to study the effects of EV‐encapsulated MALAT1 on the M1 polarization of macrophages in AP in vivo. MALAT1 was transferred into MPC‐83 cells via EVs, which promoted M1 polarization of macrophages in AP. MALAT1 competitively bound to miR‐181a‐5p, which targeted HMGB1. Moreover, MALAT1 activated the TLR4 signalling pathway by regulating HMGB1. EV‐encapsulated MALAT1 competitively bound to miR‐181a‐5p to upregulate the levels of IL‐6 and TNF‐α by regulating HMGB1 via activation of the TLR4 signalling pathway, thereby inducing M1 polarization of macrophages in AP. In vivo experimental results also confirmed that MALAT1 shuttled by EVs promoted M1 polarization of macrophages in AP via the miR‐181a‐5p/HMGB1/TLR4 axis. Overall, EV‐loaded MALAT1 facilitated M1 polarization of macrophages in AP via miR‐181a‐5p/HMGB1/TLR4, highlighting a potential target for treating AP. |
| تدمد: | 1582-4934 1582-1838 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c27df26b7f48ddb68d1f834cedeb2b07Test https://doi.org/10.1111/jcmm.16844Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c27df26b7f48ddb68d1f834cedeb2b07 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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