Regulation of Autophagy Affects the Prognosis of Mice with Severe Acute Pancreatitis

Wan, Jianhua; Chen, Jie; Wu, Dangyan; Yang, Xiaoyu; Ouyang, Yaobin; Zhu, Yin; Xia, Liang; Lü, Nonghua

doi:10.1007/s10620-018-5053-0

Cited by 14 publications

(13 citation statements)

References 33 publications

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“…In AP, impaired autophagosome maturation could activate oxidative stress and nuclear factor κB (NF-κB) pathways to aggravate the disease process 10 . In our previous results, inhibition of autophagy initiation by 3-MA could significantly reduce the severity of pancreatitis pathology and improve prognosis 11 . Based on previous studies 13 reporting that TAB2 interacts with Beclin-1 and inhibits autophagosome formation, we performed a double-staining with anti-TAB2 antibody and anti-beclin-1 to understand if TAB2 may be involved in the regulation of autophagy in our experimental settings.…”

Section: Resultsmentioning

confidence: 80%

“…The sections were processed for hematoxylin and eosin (H&E) staining. Pancreatic histopathology was scored based on Schmidt et al 19 on a scale of 0–3 in four items as previously described 11,20 : edema (0, absent; 1, focally increased between lobules; and 2, diffusely increased); inflammatory cell infiltration (0, absent; 1, in ducts or around ductal margins; 2, in the parenchyma of <50% of lobules; and 3, in the parenchyma of >50% of lobules); hemorrhage and fat necrosis (0, absent; 1, 1–2 foci; 2, 3–4 foci; and 3, >5 foci); and acinar necrosis (0, absent; 1, periductal necrosis <5%; 2, focal necrosis 5–20%; and 3, diffuse parenchymal necrosis 20–50%).…”

Section: Methodsmentioning

confidence: 99%

“…In the process, impaired autophagic flux causes an accumulation of autolysosomes in acinar cells, which leads to an increase of reactive oxygen species (ROS) due to defective clearance of damaged or depolarized mitochondria, and accumulation of p62-containing protein aggregates. In vitro or vivo, inhibition of autophagy induction by 3-MA reduced the formation of autophagosomes unable to fuse with lysosomes that are observed in cholecystokinin (CCK)-stimulated pancreatic acinar cells or cerulein-induced pancreatitis model 11,12 . Beclin-1 is a central regulator of autophagy whose activity is negatively regulated by the binding with TGF-beta activated kinase 1 (TAK1) /MAP3K7 binding protein 2 (TAB2), which is a miR-155 target protein.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model

et al. 2019

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Acute pancreatitis (AP) is a common digestive disease characterized by inflammation of the pancreas. MiR-155 plays a role in promoting inflammation and inhibiting the activation of anti-inflammatory pathways. Impaired autophagy could promote zymogen activation, abnormal acinar cell secretion, cell death, and the inflammatory response to aggravate AP. The aim of this study was to ascertain the effect of silencing miR-155 on AP through its effects on inflammation and impaired autophagy in vivo. In this study, AAV(adeno-associated virus)-mediated miR-155 and miR-155 sponge were injected through the tail vein of mice. After 3 weeks, AP was induced by intraperitoneal (IP) injections of cerulein. Pancreatic and pulmonary tissues were analyzed after 24 h. Silencing of miR-155 ameliorated pancreas and lung damage in three AP models of mice by preventing accumulation of autophagosomes that are unable to fuse with lysosomes and decreasing pancreatic inflammation by targeting TAB2. 3-MA could reduce the aberrant accumulation of autophagosomes, which alleviates the pancreas damage that was aggravated by increasing miR-155 levels. These findings demonstrate that the inhibition of miR-155 holds promise for limiting pancreatitis.

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Section: Resultsmentioning

confidence: 80%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model

et al. 2019

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“…The results suggest that the DSS induced UC symptoms in rats, which had high DAI scores, short colon ( Figure 6 ), and higher pathological scores in the tissues ( Figure 8 ). Meanwhile, the inflammatory responses and oxidative stress were also increased ( Figures 3 and 4 ), suggesting that DSS induction is an effective method to create a UC model and also used in other UC studies ( Wan et al., 2018 ; Hou et al., 2019 ; Ye et al., 2019 ).…”

Section: Discussionmentioning

confidence: 83%

Kuijieyuan Decoction Improved Intestinal Barrier Injury of Ulcerative Colitis by Affecting TLR4-Dependent PI3K/AKT/NF-κB Oxidative and Inflammatory Signaling and Gut Microbiota

Liu

Piao²,

Niu

et al. 2020

Front. Pharmacol.

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Ethnopharmacological Relevance In Traditional Chinese medicine (TCM) theory, ulcerative colitis (UC) is associated with damp-heat, blood stasis, and intestinal vascular ischemia. Kuijieyuan decoction (KD) is a traditional Chinese medicine based on the above theory and used clinically to alleviate UC injury. Methods The main components of KD were analyzed by using high-pressure liquid chromatography (HPLC) and confirmed by UPLC-MS/MS. A UC model was established in rats by using dextran sulfate sodium (DSS) and dead rats (caused by DSS) were excluded from the study. Forty-eight rats were divided into 6 groups, health control (CG), UC model (UG), sulfasalazine (SG), low-dose KD (LG), middle-dose KD (MG), and high-dose KD (HG) groups. UC damage was assessed by hematoxylin and eosin staining and scan electron microscopy. We measured Toll-like receptor 4 (TLR4), p-phosphatidylinositol 3-kinase (PI3K), PI3K, p-Protein kinase B (AKT), AKT, p-nuclear factor kappa B (NF-κB), NF-κB, oxidative stress marker (superoxidase dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx), and malondialdehyde) and inflammatory markers (tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6 and IL-10) in UC tissues. Gut microbiota was analyzed through16S rRNA sequencing. Results The main components of KD consist of gallic acid, paeoniflorin, emodin, berberine, coptisine, palmatine, jatrorrhizine, baicalein and baicalin. The UC model was successfully established by causing intestinal barrier injury with the loss of intestinal villi and destructed mitochondria of intestinal epithelial cells. Both sulfasalazine and KD treatment repaired UC injury, reduced the levels of malondialdehyde, TNFα, IL-1, IL-6, TLR4, p-PI3K, p-AKT, and p-NF-κB, and increased the levels of SOD, GPx, CAT, and IL-10. KD showed a protective function for the UC model in a dose-dependent way. The serum levels of paeoniflorin and baicalin had a strong relationship with the levels of inflammatory and oxidative stress biomarkers. KD treatment increased the proportion of Alloprevotella, Treponema, Prevotellaceae, and Prevotella, and reduced the proportion of Escherichia_Shigella and Desulfovibrio in gut microbiota. Conclusions KD improved intestinal barrier injury of ulcerative colitis, antioxidant and anti-inflammatory properties by affecting TLR4-dependent PI3K/AKT/NF-κB signaling possibly through the combination of its main compounds, and improving gut microbiota.

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“…In this issue of Digestive Diseases and Sciences, Wan et al [5] explored the therapeutic effects of altering autophagy after the onset of AP in two established mouse models of AP, the arginine and caerulein + lipopolysaccharide (LPS) models, both complicated by extrapancreatic organ injury. Injections of 3-methyladenine (3-MA) and rapamycin (RAPA) were used to modulate autophagy.…”

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confidence: 99%

Concise Commentary: The Benefits of Recycling—How Autophagy Regulation Affects Acute Pancreatitis

Deng

Dai

2018

Dig Dis Sci

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Regulation of Autophagy Affects the Prognosis of Mice with Severe Acute Pancreatitis

Abstract: Our study found that the regulation of autophagy could alter the progression of AP induced by L-arginine or cerulein plus LPS in mice.

Cited by 14 publications

References 33 publications

Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model

Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model

Kuijieyuan Decoction Improved Intestinal Barrier Injury of Ulcerative Colitis by Affecting TLR4-Dependent PI3K/AKT/NF-κB Oxidative and Inflammatory Signaling and Gut Microbiota

Concise Commentary: The Benefits of Recycling—How Autophagy Regulation Affects Acute Pancreatitis

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