Signalling mechanisms in PAF-induced intestinal failure

Lautenschläger, Ingmar; Wong, Yuk Lung; Sarau, Jürgen; Goldmann, Torsten; Zitta, Karina; Albrecht, Martín; Frerichs, Inéz; Weiler, Norbert; Uhlig, Stefan

doi:10.1038/s41598-017-13850-x

Cited by 7 publications

(7 citation statements)

References 78 publications

(90 reference statements)

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“…This conclusion was supported by Lautenschläger et al, who used PAF to stimulate Ca 2+ release downstream of IP3 and slowed down small intestinal vasoconstriction; in addition, further use of 2-aminoethoxydiphenyl borate to weaken IP3 signalling reversed this effect. 69 For this reason, the PAF–IP3–Ca 2+ signalling pathway was formed. 70 IP3 is a signalling messenger whose main role is to mobilise intracellular Ca 2+ release.…”

Section: Paf-mediated Cytokine Involvement In Nafldmentioning

confidence: 99%

Platelet-Activating Factor Promotes the Development of Non-Alcoholic Fatty Liver Disease

Yin

Shi

2022

DMSO

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Non-alcoholic fatty liver disease (NAFLD) is a multifaceted clinicopathological syndrome characterised by excessive hepatic lipid accumulation that causes steatosis, excluding alcoholic factors. Platelet-activating factor (PAF), a biologically active lipid transmitter, induces platelet activation upon binding to the PAF receptor. Recent studies have found that PAF is associated with gamma-glutamyl transferase, which is an indicator of liver disease. Moreover, PAF can stimulate hepatic lipid synthesis and cause hypertriglyceridaemia. Furthermore, the knockdown of the PAF receptor gene in the animal models of NAFLD helped reduce the inflammatory response, improve glucose homeostasis and delay the development of NAFLD. These findings suggest that PAF is associated with NAFLD development. According to reports, patients with NAFLD or animal models have marked platelet activation abnormalities, mainly manifested as enhanced platelet adhesion and aggregation and altered blood rheology. Pharmacological interventions were accompanied by remission of abnormal platelet activation and significant improvement in liver function and lipids in the animal model of NAFLD. These confirm that platelet activation may accompany a critical importance in NAFLD development and progression. However, how PAFs are involved in the NAFLD signalling pathway needs further investigation. In this paper, we review the relevant literature in recent years and discuss the role played by PAF in NAFLD development. It is important to elucidate the pathogenesis of NAFLD and to find effective interventions for treatment.

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Section: Paf-mediated Cytokine Involvement In Nafldmentioning

confidence: 99%

Platelet-Activating Factor Promotes the Development of Non-Alcoholic Fatty Liver Disease

Yin

Shi

2022

DMSO

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“…The detailed surgical procedure and ex-vivo perfusion was described by our group earlier [13,14]. Briefly, rats were anesthetized by inhalation Sevoflurane and additional intraperitoneal injection of Ketamine.…”

Section: Preparation Of the Small Intestine Cannulation And Perfusionmentioning

confidence: 99%

“…Constant flow perfusion is applied by a syringe pump (12) and roller pump (13). The vascular perfusate is prewarmed, oxygenated, and pH equilibrated with tempered hollow fiber dialyzer flushed with carbogen gas (14). Pressure transducer (15-17) allow online detection of the luminal (yellow), venous (blue) and arterial (red) pressures.…”

Section: Experimental Protocol Of the In-vivo Ipc (Iipc) Groupmentioning

confidence: 99%

“…In the actual study we have employed a perfused model of the rat small intestine [13,14] to evaluate physiological and cellular effects of intestinal I/R-injury and to compare the influence of in-vivo IPC (iIPC) with ex-vivo IPC (eIPC), in which blood derived factors and nerval regulations are excluded. We hypothesize that iIPC and eIPC differentially affect physiological as well as cellular events triggered by intestinal I/R-injury.…”

Section: Plos Onementioning

confidence: 99%

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Effects of different ischemic preconditioning strategies on physiological and cellular mechanisms of intestinal ischemia/reperfusion injury: Implication from an isolated perfused rat small intestine model

et al. 2021

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Background Intestinal ischemia/reperfusion (I/R)-injury often results in sepsis and organ failure and is of major importance in the clinic. A potential strategy to reduce I/R-injury is the application of ischemic preconditioning (IPC) during which repeated, brief episodes of I/R are applied. The aim of this study was to evaluate physiological and cellular effects of intestinal I/R-injury and to compare the influence of in-vivo IPC (iIPC) with ex-vivo IPC (eIPC), in which blood derived factors and nerval regulations are excluded. Methods Using an established perfused rat intestine model, effects of iIPC and eIPC on physiological as well as cellular mechanisms of I/R-injury (60 min hypoxia, 30 min reperfusion) were investigated. iIPC was applied by three reversible occlusions of the mesenteric artery in-vivo for 5 min followed by 5 min of reperfusion before isolating the small intestine, eIPC was induced by stopping the vascular perfusion ex-vivo 3 times for 5 min followed by 5 min of reperfusion after isolation of the intestine. Study groups (each N = 8–9 animals) were: iIPC, eIPC, I/R (iIPC group), I/R (eIPC group), iIPC+I/R, eIPC+I/R, no intervention/control (iIPC group), no intervention/control (eIPC group). Tissue morphology/damage, metabolic functions, fluid shifts and barrier permeability were evaluated. Cellular mechanisms were investigated using signaling arrays. Results I/R-injury decreased intestinal galactose uptake (iIPC group: p<0.001), increased vascular perfusion pressure (iIPC group: p<0.001; eIPC group: p<0.01) and attenuated venous flow (iIPC group: p<0.05) while lactate-to-pyruvate ratio (iIPC group, eIPC group: p<0.001), luminal flow (iIPC group: p<0.001; eIPC group: p<0.05), goblet cell ratio (iIPC group, eIPC group: p<0.001) and apoptosis (iIPC group, eIPC group: p<0.05) were all increased. Application of iIPC prior to I/R increased vascular galactose uptake (P<0.05) while eIPC had no significant impact on parameters of I/R-injury. On cellular level, I/R-injury resulted in a reduction of the phosphorylation of several MAPK signaling molecules. Application of iIPC prior to I/R increased phosphorylation of JNK2 and p38δ while eIPC enhanced CREB and GSK-3α/β phosphorylation. Conclusion Intestinal I/R-injury is associated with major physiological and cellular changes. However, the overall influence of the two different IPC strategies on the acute phase of intestinal I/R-injury is rather limited.

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“…Smokers and patients with COPD have been shown to have increased expression of PAFR. This may explain why patients with COPD are more likely to have chronic and invasive infections with Streptococcus pneumoniae and Haemophilus influenzae [34,35].…”

Section: Lungsmentioning

confidence: 99%

PAF Physiology in Target Organ Systems—A Deep Dive to Understand the PAF Mystery in Pathogenesis of Disease

Shah

Kumar

Shah

2021

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The purpose of this literature review is to gain an overview of the role of platelet-activating factor (PAF) within each of the body systems and how it contributes to normal and pathophysiological states. The review showed that there are multiple functions of PAF that are common to several body systems; however, there is little evidence to explain why PAF has this affect across multiple systems. Interestingly, there seems to be conflicting research as to whether PAF is an overall protective or pathogenic pathway. Within this research, it was found that there are different pathways depending on the specific body system, as well as between body systems. However, one universal function reported in the literature is of PAF as a pro-inflammatory molecule. Overall, this review identified five major functions of PAF: vasoconstriction, increased inflammation, vascular remodeling, increased edema, and endothelial permeability.

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Signalling mechanisms in PAF-induced intestinal failure

Cited by 7 publications

References 78 publications

Platelet-Activating Factor Promotes the Development of Non-Alcoholic Fatty Liver Disease

Platelet-Activating Factor Promotes the Development of Non-Alcoholic Fatty Liver Disease

Effects of different ischemic preconditioning strategies on physiological and cellular mechanisms of intestinal ischemia/reperfusion injury: Implication from an isolated perfused rat small intestine model

PAF Physiology in Target Organ Systems—A Deep Dive to Understand the PAF Mystery in Pathogenesis of Disease

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