Fibroblast Growth Factor (FGF) Signaling Protects Against Acute Pancreatitis-Induced Damage by Modulating Inflammatory Responses

Abstract

Science and Technology Plan Projects of Putian City (2018s3001) Background:Acute pancreatitis (AP) is a symptom of sudden pancreas inflammation, which causes patients severe suffering.In general, fibroblast growth factor (FGF) levels are increased and amylase and lipase activities are elevated during AP pathogenesis, but protein concentration are low. However, the mechanism through which FGF signaling regulates AP pathogenesis remains elusive. Material/Methods:The concentrations of PGE2, TNF-a, sCRP, FGF1, and FGF2 in the serum samples of the AP group and healthy control group were detected by enzyme-linked immunosorbent assay. In addition, IkBa and p-IkBa levels were analyzed in the serum samples. Subsequently, the AP rat model was established, and FGF1, FGF2, anti-FGF1, and anti-FGF2 antibodies and Bay11-7082 were injected into AP rats. TNF-a, PAI-1 JNK, p-JNK, IkBa, and p-IkBa levels were also examined. Results:Results showed that levels of PGE2, TNF-a, sCRP, p-IkBa, FGF1, and FGF2, as well as amylase and lipase activity were increased in patients with AP compared with those in healthy people. In addition, protein concentrations were lower in patients with AP than in the healthy group. Activation of FGF signaling by injecting FGF1 or FGF2 also inhibited AP-induced inflammation response in the pancreas and increased amylase and lipase activities, as well as protein concentration. However, the injection of FGF1 and FGF2 antibodies accelerated APmediated inflammation responses in the serum. In addition, Bay11-7082 injection inhibited AP activation of inflammation response and amylase and lipase activities. Protein concentration were also increased in AP rats. Conclusions:FGF signaling protects against AP-mediated damage by inhibition of AP-activating inflammatory responses.

New developments in the biology of fibroblast growth factors

“…Injection of recombinant FGF1 or FGF2 in rats with AP was shown to inhibit inflammation and the production of inflammatory cytokines and normalize amylase and lipase activities. In contrast, the injection of FGF1 and FGF2 inhibitory antibodies worsened the AP phenotype (Tu et al, 2020).…”

Cellular Mechanisms of FGF-Stimulated Tissue Repair

“…For example, the herpes virus-mediated overexpression of FGF2 in rat hippocampus attenuated the increase of IL1β expression associated with artificially induced epileptogenesis [ 135 ]. FGF1 or FGF2 administration decreased the inflammatory responses associated with acute pancreatitis in mice [ 136 ]. Furthermore, FGF1 administration decreased the secretion of TNFα and IL6 in a mouse model of diet-induced obesity [ 137 ], and this effect stemmed from the suppression of pro-inflammatory JNK signaling.…”

Routine laboratory parameters in patients with necrotizing pancreatitis by the time of operative pancreatic debridement: Food for thought

“…Fibroblast recruitment into the necrotic area is orchestrated by the coordinated effect of numerous cytokines and growth factors. Among others, fibroblast growth factor and platelet-derived growth factor (PDGF) are the major cytokines that initiate and afterward support fibroblast proliferation and chemotactic activity resulting in the necrotic area encapsulation[ 26 - 28 ]. Clinical observations of Stojek et al [ 29 ] indirectly confirmed this assumption.…”