GSK-3β activates NF-κB to aggravate caerulein-induced early acute pancreatitis in mice

Abstract

Background: Acute pancreatitis is a life-threatening disease which causes considerable morbidity and mortality. However, no specific and effective treatments are currently available for this critical condition, which is mainly due to the insufficient understanding of the early cellular events in the initial phase of acute pancreatitis. Previous researchers have reported that two independent events, intra-acinar trypsinogen and NF-κB activation, are of equal importance in the early development of acute pancreatitis. GSK-3β, an essential molecule in multiple physiopathological processes including inflammation, is associated with the expression of the NF-κB pathway.Methods: We investigated whether GSK-3β affected the expression of cytokines produced by intra-acinar cells and aimed to determine the probable regulatory mechanism by using single allele GSK-3β-deficient mice.Results: Our data showed that IL-6 and TNF-α mRNA expression in pancreatic tissue and serum IL-6 and TNF-α were significantly decreased. Meanwhile, pancreatic phospho-NF-κB p65 (ser536) protein expression in GSK-3β +/− mice was lower than that in wild type (WT) mice.Conclusions: GSK-3β may activate intra-acinar NF-κB signaling to promote the production of proinflammatory cytokines, which then induces the recruitment of inflammatory cells and activation of the cytokine cascade, further promoting local and systemic inflammation and ultimately aggravating acute pancreatitis. These findings strongly indicate that GSK-3β may be a potential treatment target for acute pancreatitis.

Curcumin relieves oxaliplatin‐induced neuropathic pain via reducing inflammation and activating antioxidant response

“…GSK‐3β activation promotes proinflammatory response (Fu et al, 2021) and invokes oxidative damage (Wang et al, 2009) and its activation depends on the phosphorylation at Tyr216. The intensity and expression level of spinal pGSK‐3β‐Tyr216 was greatly increased in OXA group with intensity value at 2.00 ± 0.17 (Figure 4d,e) and gray value at 2.02 ± 0.21 (Figure 4f,g).…”

Astragalus polysaccharide improves diabetic ulcers by promoting M2-polarization of macrophages to reduce excessive inflammation via the β-catenin/ NF-κB axis at the late phase of wound-healing

“…GSK-3β dysregulation was crucial in the pathogenesis of inflammatory diseases, including diabetic wound-healing [ 35 ], and was found to regulate the inflammatory response via Wnt/β-catenin/NF-κB axis [ 36 ]. It was reported that GSK-3β inhibited Wnt/β-catenin signaling pathway [ 37 ], while activating NF-κB [ 38 ]. Moreover, silencing β-catenin promoted the expression of NF-κB [ 39 ].…”

LRFN2 binding to NMDAR inhibits the progress of ESCC via regulating the Wnt/β‐Catenin and NF‐κB signaling pathway

“…However, after knocking down LRFN2, the expression of NF‐κB and BCL2 increased. Studies have shown that GSK3B can stimulate the NF‐κB pathway, 37 , 38 , 39 so we hypothesized whether LRFN2 could affect the NF‐κB pathway due to changes in p ‐GSK3B (SER389), thereby affecting the occurrence of ESCC. This means that LRFN2 affects both the WNT and NF‐κB signaling pathways through GRIN2B, and the key molecule is GSK3β.…”