Fisetin attenuates cerulein-induced acute pancreatitis through down regulation of JNK and NF-κB signaling pathways

Jo, Il‐Joo; Bae, Gi‐Sang; Choi, Sun Bok; Kim, Dong-Goo; Shin, Joon-Yeon; Seo, Sang‐Woo; Choi, Mee-Ok; Kim, Tae-Hyeon; Song, Ho‐Joon; Park, Sung‐Joo

doi:10.1016/j.ejphar.2014.05.018

Cited by 29 publications

(17 citation statements)

References 24 publications

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“…The results of the current study demonstrated that caerulein led to the activation of NF-κB signaling in AR42J cells by decreasing IKBα and increasing p50 and p65, indicating that NF-κB pathway activation was involved in AP progression. Inhibition of NF-κB signaling has been regarded as a key avenue for therapeutics of AP (41)(42)(43). Additionally, the results suggested that miR-9 inhibited the caerulein-induced activation of the NF-κB pathway, which has also been reported in previous work (16).…”

Section: Discussionsupporting

confidence: 81%

miR‑9 alleviated the inflammatory response and apoptosis in caerulein‑induced acute pancreatitis by regulating FGF10 and the NF‑κB signaling pathway

et al. 2021

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MicroRNAs (miRs) have been implicated in the development of acute pancreatitis (AP). However, the role and potential mechanism of miR-9 in AP progression remains unclear. Caerulein-treated AR42J cells were used as a cellular model of AP. Results revealed caerulein triggered an inflammatory response by promoting the secretion of inflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 1β and IL-6], as evidenced by ELISA. Furthermore, caerulein-induced apoptosis was reported by flow cytometry and western blot assays. Additionally, miR-9 expression was downregulated by caerulein treatment, as demonstrated by reverse transcription quantitative PCR. However, miR-9 overexpression reduced the inflammatory response and apoptosis in caerulein-treated AR42J cells. miR-9 knockdown resulted in opposite effects. Furthermore, fibroblast growth factor (FGF) 10 was validated to be targeted via miR-9 by luciferase, RNA immunoprecipitation and RNA pull-down assays. Results demonstrated increased FGF10 expression in caerulein-treated AR42J cells and that FGF10 over expression exacerbated the caerulein-induced inflammatory response and apoptosis, while its knockdown had the opposite effect. Additionally, FGF10 reversed the effect of miR-9 on caerulein-induced injury in AR42J cells. Results demonstrated that miR-9 inhibited the expression of the nuclear factor κB (NF-κB) pathway-related proteins by downregulating FGF10. As a result, miR-9 decreased inflammatory response and apoptosis in caerulein-treated AR42J cells by targeting FGF10 and blocking NF-κB signaling, suggesting that miR-9 may serve as a novel target for AP treatment.

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Section: Discussionsupporting

confidence: 81%

miR‑9 alleviated the inflammatory response and apoptosis in caerulein‑induced acute pancreatitis by regulating FGF10 and the NF‑κB signaling pathway

et al. 2021

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“…The levels of edema and proinflammatory cell infiltration were scored on a scale of 0 to 3 with 0 considered normal and 3 as severe. 23,24 2.9 | Wet-to-dry weight ratio…”

Section: Hematoxylin and Eosin Stainingmentioning

confidence: 99%

Retracted: microRNA‐542‐5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen‐activated protein kinase signaling pathway through the negative regulation of P21‐activated kinase 1

Wang

et al. 2018

J of Cellular Biochemistry

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Severe acute pancreatitis (SAP) is a condition associated with high rates of mortality and lengthy hospital stays. In the current study, SAP mouse models were established in BALB/c wild-type and P21-activated kinase 1 (PAK1) knockdown mice with the objective of determining the expression of microRNA-542-5p (miR-542-5p) and the subsequent elucidation of the mechanism by which it influences acute lung injury (ALI) by mediating mitogen-activated protein kinase (MAPK) signaling and binding to PAK1. The targeting relationship between miR-542-5p and PAK1 was verified using the bioinformatics prediction website and by the means of a dual-luciferase reporter assay. Following the SAP model establishment, the mice were assigned into various groups with the introduction of different mimic and inhibitors in an attempt to investigate the effects involved with miR-542-5p on inflammatory reactions among mice with SAP-associated ALI. Our results indicated that PAK1 was targeted and negatively mediated by miR-542-5p. Mice with SAP-associated ALI exhibited an increased wet-to-dry weight ratio, myeloperoxidase activity, serum amylase activity, TNF-α, interleukin-1 beta (IL-1β), and intercellular adhesion molecule-1 (ICAM-1) contents, p-p38MAPK, p-ERK1/2, and p-JNK protein levels as well as PAK1 positive expression, while decreased miR-542-5p levels were observed. Functionally, overexpression of miR-542-5p improves ALI in mice with SAP via inhibition of the MAPK signaling pathway by binding to PAK1.Based on the evidence from experimental models, miR-542-5p was shown to improve ALI among mice with SAP, while suggesting that the effect may be related to the inactivation of the MAPK signaling pathway and downregulation of PAK1 gene. Thus, miR-542-5p could serve as a promising target for ALI treatment.

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“…After decapitating of mice, a portion of pancreases was fixed in 10% formalin for 24-48 h. Then, pancreases were embedded in paraffin to be cut into 5 mm-thick sections and dying with hematoxylin and eosin. Finally, a pathologist observed the tissue sections under light microscope blindly and scored them (1-4) through evaluating the following criteria: edema, pro-inflammatory cell infiltration, acinar vacuolization and necrosis (one is normal and 4 is severe) [25].…”

Section: Histopathological Examination and Scoringmentioning

confidence: 99%

Protective effects of tropisetron on cerulein-induced acute pancreatitis in mice

Rahimian

Zirak

Seyedabadi

et al. 2017

Biomedicine & Pharmacotherapy

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Acute pancreatitis (AP) causes morbidity and mortality. The aim of the present study was to investigate the protective effect of tropisetron against AP induced by cerulein. Cerulein (50μg/kg, 5 doses) was used to induce AP in mice. Six hours after final cerulein injection, animals were decapitated. Hepatic/pancreatic enzymes in the serum, pancreatic content of malondialdehyde (MDA), pro-inflammatory cytokines and myeloperoxidase (MPO) activity were measured. Tropisetron significantly attenuated pancreatic injury markers and decreased the amount of elevated serum amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), MPO activities and pro-inflammatory cytokines levels caused by AP in mice. Tropisetron didn't affect the pancreatic levels of MDA. Our results suggest that tropisetron could attenuate cerulein-induced AP by combating inflammatory signaling. Further clinical studies are needed to confirm its efficacy in patients with AP.

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Fisetin attenuates cerulein-induced acute pancreatitis through down regulation of JNK and NF-κB signaling pathways

Cited by 29 publications

References 24 publications

miR‑9 alleviated the inflammatory response and apoptosis in caerulein‑induced acute pancreatitis by regulating FGF10 and the NF‑κB signaling pathway

miR‑9 alleviated the inflammatory response and apoptosis in caerulein‑induced acute pancreatitis by regulating FGF10 and the NF‑κB signaling pathway

Retracted: microRNA‐542‐5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen‐activated protein kinase signaling pathway through the negative regulation of P21‐activated kinase 1

Protective effects of tropisetron on cerulein-induced acute pancreatitis in mice

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