Quercetin inhibits caerulein-induced acute pancreatitis through regulating miR-216b by targeting MAP2K6 and NEAT1
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Inflammopharmacology
ORIGINAL ARTICLE
Quercetin inhibits caerulein‑induced acute pancreatitis through regulating miR‑216b by targeting MAP2K6 and NEAT1 Bo Sheng1 · Lei Zhao1 · Xuefeng Zang1 · Jie Zhen1 · Yang Liu1 · Weishuai Bian1 · Wei Chen1 Received: 27 July 2020 / Accepted: 29 September 2020 © Springer Nature Switzerland AG 2020
Abstract Acute pancreatitis (AP) is a common acute abdominal disease with high mortality and mortality rates. Increasing evidences clarified that Traditional Chinese Medicine (TCM) adjuvant therapy for AP can be used and it gives a positive effect. Quercetin (3,3′,4′,5,7-pentahydroxyflavone, QE) is a type of flavone compound with positive effect on cancer and inflammation prevention. The current study aims to identify the effect of QE on AP and potential molecular effect. In this case, caerulein (CAE) induced AP cell and mice model were used. QE alleviated inflammatory mediators TNF-α, IL-6, and IL-10 in experiments. In addition, miR-216b was increased based on QE treatment. In further study, MAP2K6 of p38/MAPK signaling pathway was identified as a direct target of miR-216b, and QE inhibited p38/MAPK signaling pathway through up-regulating miR-216b. Our study also first confirmed that long non-coding RNA NEAT1 is a direct target of miR-216b and can be suppressed by QE. Because of the target, NEAT1, miR-216b, and MAP2K6 formed a competitive endogenous RNA (ceRNA) network. Besides direct target mediated by QE, it also decreased TNF-α which down-regulated TRAF2 and MAP3K5 located on upstream of p38/MAPK signaling and formed a feedback loop. In conclusion, QE has a protective effect on AP through inhibiting p38/MAPK signaling pathway by up-regulating miR-216b and suppressing TNF-α. Keywords Quercetin · miR-216b · MAP2K6 · p38/MAPK signaling · NEAT1 · Acute pancreatitis
Introduction Acute pancreatitis (AP) is a common acute abdominal disease with high mortality and mortality rates, and is mainly caused by the excessive activation of pancreatic digestive enzymes in clinical acute abdomen (Pandol et al. 2007). According to statistics, there were 220,000 inpatients with AP in USA in 2013; among these cases, 1661 were critically ill (Dike et al. 2020). Additionally, the overall mortality rate of AP patients is about 5% and that in patients with necrotizing pancreatitis is around 17% (Cofaru et al. 2020). At present, several clinical treatments, including conservative and aggressive treatments, have been used to treat AP, yet a more specific treatment or therapy is needed. Recently, increasing evidence clarifies the positive effect of traditional
* Wei Chen [email protected] 1
Department of Intensive Care Unit, Beijing Shijitan Hospital Affiliated to Capital Medical University, No. 10 Tieyilu Street, Beijing 100038, People’s Republic of China
Chinese medicine (TCM) adjuvant therapy on the treatment of AP (Li et al. 2017). Accumulating studies reveal that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) participate in regulating AP formation and progression (Yang et al. 2020
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