Effect of TRAF6 in acute pancreatitis-induced intestinal barrier injury via TLR4/NF-κB signal pathway

Wei, Biwei; Wu, Qing; Yang, Xue‐Xia; Lai, Chen; Zhou, Shanshan; Liang, Zhihai

doi:10.1016/j.tice.2022.101792

Cited by 8 publications

(4 citation statements)

References 40 publications

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“…There was a significant weight gain in the treated group compared to the non-treated group ( Figure 4 B). When the integrity of the intestinal barrier is damaged, diamine oxidase, D-lactate and bacterial endotoxin are released into the blood [ 26 , 27 ]. We monitored these markers in the blood from tail vein and found them increased in psychologically stressed rat on day 7 ( Figure S2 ), and decreased when treated with JM25-1 on day 11 ( Figure 4 C).…”

Section: Resultsmentioning

confidence: 99%

A Novel Mast Cell Stabilizer JM25-1 Rehabilitates Impaired Gut Barrier by Targeting the Corticotropin-Releasing Hormone Receptors

Sun

Liu

et al. 2022

Pharmaceuticals

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Mast cell (MC) plays a central role in intestinal permeability; however, few MC-targeting drugs are currently available for protection of the intestinal barrier in clinical practice. A nonfluorinated Lidocaine analog 2-diethylamino-N-2,5-dimethylphenyl acetamide (JM25-1) displays anti-allergic effect, but its impact on MC remains elusive. In this study, we explored whether JM25-1 has therapeutic potential on intestinal barrier defect through stabilizing MC. JM25-1 alleviated release of β-hexosaminidase and cytokine production of MC. The paracellular permeability was redressed by JM25-1 in intestinal epithelial cell monolayers co-cultured with activated MC. In vivo, JM25-1 diminished intestinal mucosal MC amount and cytokine production, especially downregulating the expression of CRHR1, accompanied by an increase of CRHR2. Protective effects appeared in JM25-1-treated stress rats with a recovery of weight and intestinal barrier integrity. Through network pharmacology analysis, JM25-1 showed a therapeutic possibility for irritable bowel syndrome (IBS) with predictive targeting on PI3K/AKT/mTOR signaling. As expected, JM25-1 reinforced p-PI3K, p-AKT, p-mTOR signaling in MC, while the mTOR inhibitor Rapamycin reversed the action of JM25-1 on the expression of CRHR1 and CRHR2. Moreover, JM25-1 successfully remedied intestinal defect and declined MC and CRHR1 expression in rat colon caused by colonic mucus of IBS patients. Our data implied that JM25-1 possessed therapeutic capacity against intestinal barrier defects by targeting the CRH receptors of MC through PI3K/AKT/mTOR signaling.

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Section: Resultsmentioning

confidence: 99%

A Novel Mast Cell Stabilizer JM25-1 Rehabilitates Impaired Gut Barrier by Targeting the Corticotropin-Releasing Hormone Receptors

Sun

Liu

et al. 2022

Pharmaceuticals

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“…SD rats have been widely accepted as subjects of AP since 1952 29 , and most patients with HTGP were male 30 . Besides, our team has rich experience in using male SD rats to establish AP or HTGP models in vivo 14,24,[31][32][33] . Hence, male SD rats were used to establish HTGP model in the study.…”

Section: Discussionmentioning

confidence: 99%

Liproxstatin-1 attenuates acute hypertriglyceridemic pancreatitis through inhibiting ferroptosis in rats

Xiang,

Xu,

Liu

et al. 2024

Sci Rep

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Ferroptosis is closely associated with inflammatory diseases, including acute pancreatitis (AP); however, the involvement of ferroptosis in hypertriglyceridemic pancreatitis (HTGP) remains unclear. In the present study, we aimed to explore the relationship between lipid metabolism and ferroptosis in HTGP and the alleviating effect of liproxstatin-1 (Lip-1) in vivo. This study represents the first exploration of lipid metabolism and endoplasmic reticulum stress (ERS) in HTGP, targeting ferroptosis as a key factor in HTGP. Hypertriglyceridemia (HTG) was induced under high-fat diet conditions. Cerulein was then injected to establish AP and HTGP models. Lip-1, a specific ferroptosis inhibitor, was administered before the induction of AP and HTGP in rats, respectively. Serum triglyceride, amylase, inflammatory factors, pathological and ultrastructural structures, lipid peroxidation, and iron overload indicators related to ferroptosis were tested. Moreover, the interaction between ferroptosis and ERS was assessed. We found HTG can exacerbate the development of AP, with an increased inflammatory response and intensified ferroptosis process. Lip-1 treatment can attenuate pancreatic injury by inhibiting ferroptosis through lipid metabolism and further resisting activations of ERS-related proteins. Totally, our results proved lipid metabolism can promote ferroptosis in HTGP by regulating ACSL4/LPCAT3 protein levels. Additionally, ERS may participate in ferroptosis via the Bip/p-EIF2α/CHOP pathway, followed by the alleviating effect of Lip-1 in the rat model.

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“…Increased expression of IL-1β, IL-6, IL-12, and TNF-α has been detected in active UC, and this increased expression is associated with the severity of inflammation [ [31] , [32] , [33] ]. A number of studies have shown that TLR4 is the main mediator of the LPS response [ [34] , [35] , [36] ], and TLR4 signal transduction can promote intestinal injury in DSS-induced or TNBS-induced colitis [ [37] , [38] , [39] ]. We had verified the increased expression of TLR4 in clinical intestinal mucosa specimens from patients with GC-resistant UC, which was negatively correlated with the expression level of miR-642a-5p [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

miR-642a-5p increases glucocorticoid sensitivity by suppressing the TLR4 signalling pathway in THP-1 cells

Luo

Wang

Xiao

et al. 2022

Biochemistry and Biophysics Reports

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Effect of TRAF6 in acute pancreatitis-induced intestinal barrier injury via TLR4/NF-κB signal pathway

Cited by 8 publications

References 40 publications

A Novel Mast Cell Stabilizer JM25-1 Rehabilitates Impaired Gut Barrier by Targeting the Corticotropin-Releasing Hormone Receptors

A Novel Mast Cell Stabilizer JM25-1 Rehabilitates Impaired Gut Barrier by Targeting the Corticotropin-Releasing Hormone Receptors

Liproxstatin-1 attenuates acute hypertriglyceridemic pancreatitis through inhibiting ferroptosis in rats

miR-642a-5p increases glucocorticoid sensitivity by suppressing the TLR4 signalling pathway in THP-1 cells

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