Necroptosis: a potential, promising target and switch in acute pancreatitis

Wang, Gang; Qu, Feng-zhi; Li, Le; Lv, Jiachen; Sun, Bei

doi:10.1007/s10495-015-1192-3

Cited by 51 publications

(41 citation statements)

References 83 publications

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“…Apoptosis, displaying chromatin aggregation, nuclear condensation, and chromosomal DNA fragmentation, is executed by caspases orchestrating cellular destruction with proteolytic cascades [5]. Necrosis, exhibiting cytoplasmic swelling and disruption of the plasma membrane, is positively correlated with the severity of acute pancreatitis [6]. Milder forms of experimental pancreatitis in rats induced by supramaximal doses of caerulein are characterized by high numbers of apoptotic cells and low numbers of necroptotic cells [7,8].…”

Section: Introductionmentioning

confidence: 99%

RNA-Seq Analyses of the Role of miR-21 in Acute Pancreatitis

Lin

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Our previous study demonstrated that a deficiency of microRNA 21 (miR-21) protects mice from acute pancreatitis, yet the underlying molecular networks associated with miR-21 in pancreatitis and pancreatitis-associated lung injury remain unexplored. Methods: We used next generation sequencing to analyze gene expression profiles of pancreatic tissues from wild-type (WT) and miR-21 knockout (KO) mice treated with caerulein by using a 1-day treatment protocol. The Database for Annotation, Visualization, and Integrated Discovery gene annotation tool and Ingenuity Pathway Analysis were used to analyze the molecular pathways, while quantitative real-time PCR, western blotting, and immunohistochemistry were used to explore the molecular mechanisms. Results: We identified 152 differentially expressed genes (DEGs) in pancreata between WT and KO mice treated with caerulein. Cellular biogenesis and metabolism were the major pathways affected between WT and KO mice, whereas cell death and inflammatory response discriminated between WT and KO mice under acute pancreatitis. We validated 16 DEGs, consisting of 6 upregulated genes and 10 downregulated genes, involved in pancreatic injury. In particular, the upregulation of Pias3 and downregulation of Hmgb1 in KO pancreata coincided with a reduced severity of pancreatitis. In addition, we found Hmgb1 stimulation resulted in the overexpression of miR-21 in peripheral blood mononuclear cells, and deletion of miR-21 led to a reduction of caerulein-induced acute pancreatitis-associated lung injury by repressing Hmgb1 expression. Conclusion: Our data support the hypothesis that miR-21 modulates the inflammatory response during acute pancreatitis through the upregulation of Pias3 and downregulation of Hmgb1. Our findings further underscore a role for miR-21 in the promotion of acute pancreatitis.

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Section: Introductionmentioning

confidence: 99%

RNA-Seq Analyses of the Role of miR-21 in Acute Pancreatitis

Lin

Wang

et al. 2018

Cell Physiol Biochem

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“…PCD can be further classified into apoptosis, autophagy, programmed necrosis (necroptosis), and pyroptosis (Cabon et al, 2013;Shalini et al, 2015). Recent studies demonstrate that PCD is involved in inflammatory responses (Deretic et al, 2015;Wang et al, 2016). However, its role in periodontitis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Programmed cell death in periodontitis: recent advances and future perspectives

et al. 2016

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Periodontitis is a highly prevalent infectious disease, characterized by destruction of the periodontium, and is the main cause of tooth loss. Periodontitis is initiated by periodontal pathogens, while other risk factors including smoking, stress, and systemic diseases aggravate its progression. Periodontitis affects many people worldwide, but the molecular mechanisms by which pathogens and risk factors destroy the periodontium are unclear. Programmed cell death (PCD), different from necrosis, is an active cell death mediated by a cascade of gene expression events and can be mainly classified into apoptosis, autophagy, necroptosis, and pyroptosis. Although PCD is involved in many inflammatory diseases, its correlation with periodontitis is unclear. After reviewing the relevant published articles, we found that apoptosis has indeed been reported to play a role in periodontitis. However, the role of autophagy in periodontitis needs further verification. Additionally, implication of necroptosis or pyroptosis in periodontitis remains unknown. Therefore, we recommend future studies, which will unravel the pivotal role of PCD in periodontitis, allowing us to prevent, diagnose, and treat the disease, as well as predict its outcomes.

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“…Acute pancreatitis (AP) is an abdominal emergency with considerable morbidity and mortality because of its concomitant organ failures and other eventful complications . Although the exact mechanisms involved in the pathogenesis of AP have not been well elucidated, accumulation of cytoplasmic vacuoles and pre‐mature activation of trypsinogen within acini were long noticed as the two early‐phase features of AP.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen sulphide exacerbates acute pancreatitis by over‐activating autophagy viaAMPK/mTOR pathway

et al. 2016

J Cellular Molecular Medi

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Previously, we have shown that hydrogen sulphide (H2S) might be pro‐inflammatory during acute pancreatitis (AP) through inhibiting apoptosis and subsequently favouring a predominance of necrosis over apoptosis. In this study, we sought to investigate the detrimental effects of H2S during AP specifically with regard to its regulation on the impaired autophagy. The incubated levels of H2S were artificially intervened by an administration of sodium hydrosulphide (NaHS) or DL‐propargylglycine (PAG) after AP induction. Accumulation of autophagic vacuoles and pre‐mature activation of trypsinogen within acini, which indicate the impairment of autophagy during AP, were both exacerbated by treatment with NaHS but attenuated by treatment with PAG. The regulation that H2S exerted on the impaired autophagy during AP was further attributed to over‐activation of autophagy rather than hampered autophagosome–lysosome fusion. To elucidate the molecular mechanism that underlies H2S‐mediated over‐activation of autophagy during AP, we evaluated phosphorylations of AMP‐activated protein kinase (AMPK), AKT and mammalian target of rapamycin (mTOR). Furthermore, Compound C (CC) was introduced to determine the involvement of mTOR signalling by evaluating phosphorylations of downstream effecters including p70 S6 kinase (P70S6k) and UNC‐51‐Like kinase 1 (ULK1). Our findings suggested that H2S exacerbated taurocholate‐induced AP by over‐activating autophagy via activation of AMPK and subsequently, inhibition of mTOR. Thus, an active suppression of H2S to restore over‐activated autophagy might be a promising therapeutic approach against AP‐related injuries.

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Necroptosis: a potential, promising target and switch in acute pancreatitis

Cited by 51 publications

References 83 publications

RNA-Seq Analyses of the Role of miR-21 in Acute Pancreatitis

RNA-Seq Analyses of the Role of miR-21 in Acute Pancreatitis

Programmed cell death in periodontitis: recent advances and future perspectives

Hydrogen sulphide exacerbates acute pancreatitis by over‐activating autophagy viaAMPK/mTOR pathway

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