Fighting Fire with Fire: Exosomes and Acute Pancreatitis-Associated Acute Lung Injury

Abstract

Acute pancreatitis (AP) is a prevalent clinical condition of the digestive system, with a growing frequency each year. Approximately 20% of patients suffer from severe acute pancreatitis (SAP) with local consequences and multi-organ failure, putting a significant strain on patients’ health insurance. According to reports, the lungs are particularly susceptible to SAP. Acute respiratory distress syndrome, a severe type of acute lung injury (ALI), is the primary cause of mortality among AP patients. Controlling the mortality associated with SAP requires an understanding of the etiology of AP-associated ALI, the discovery of biomarkers for the early detection of ALI, and the identification of potentially effective drug treatments. Exosomes are a class of extracellular vesicles with a diameter of 30–150 nm that are actively released into tissue fluids to mediate biological functions. Exosomes are laden with bioactive cargo, such as lipids, proteins, DNA, and RNA. During the initial stages of AP, acinar cell-derived exosomes suppress forkhead box protein O1 expression, resulting in M1 macrophage polarization. Similarly, macrophage-derived exosomes activate inflammatory pathways within endothelium or epithelial cells, promoting an inflammatory cascade response. On the other hand, a part of exosome cargo performs tissue repair and anti-inflammatory actions and inhibits the cytokine storm during AP. Other reviews have detailed the function of exosomes in the development of AP, chronic pancreatitis, and autoimmune pancreatitis. The discoveries involving exosomes at the intersection of AP and acute lung injury (ALI) are reviewed here. Furthermore, we discuss the therapeutic potential of exosomes in AP and associated ALI. With the continuous improvement of technological tools, the research on exosomes has gradually shifted from basic to clinical applications. Several exosome-specific non-coding RNAs and proteins can be used as novel molecular markers to assist in the diagnosis and prognosis of AP and associated ALI.

Emodin Ameliorates Severe Acute Pancreatitis-Associated Acute Lung Injury in Rats by Modulating Exosome-Specific miRNA Expression Profiles

“…In a previously published review, we elucidated the ambivalent function of exosome-specific miRNAs in acute pancreatitis, which can be likened to a double-edged sword. 6 Following the onset of SAP, it has been observed that inflammatory cells, including macrophages and neutrophils, can release exosome-specific inflammatory miRNAs. This release can damage the pancreas and exacerbate dysfunction in extrapancreatic organs such as the intestine and lungs.…”

“…Exo-specific miRNAs obtained from serum, plasma, and ascites significantly impact the onset and progression of SAP by modulating posttranscriptional modification and inflammatory cell signaling Exo-specific miRNAs also have the potential to serve as diagnostic markers and therapeutic agents for SAP. 6 Emodin (EMO) is an anthraquinone derivative that is abundantly present in Rheum palmatum L., Polygonum multiflorum Thunb., and Polygonum cuspidatum Siebold & Zucc. 7 The solubility characteristics of EMO indicate that it is soluble in alcohol and alkali solutions while exhibiting almost negligible solubility in water.…”

A bibliometric analysis of non-coding RNA studies in acute pancreatitis

“…Search terms #1 TS = ("Pancreatitis" OR "Pancreatitis, Acute Edematous" OR "Acute Edematous Pancreatitides" OR "Edematous Pancreatitides, Acute" OR "Edematous Pancreatitis, Acute" OR "Pancreatitides, Acute Edematous" OR "Acute Edematous Pancreatitis" OR "Pancreatic Parenchymal Edema" OR "Edema, Pancreatic Parenchymal" OR "Pancreatic Parenchymal Edemas" OR "Parenchymal Edema, Pancreatic" OR "Pancreatic Parenchyma with Edema" OR "Pancreatitis, Acute" OR "Acute Pancreatitis" OR "Acute Pancreatitides" OR "Pancreatitides, Acute" OR "Peripancreatic Fat Necrosis" OR "Fat Necrosis, Peripancreatic" OR "Necrosis, Peripancreatic Fat" OR "Peripancreatic Fat Necroses") #2 TS = ("Non-coding RNA" OR "microRNA" OR "microRNAs" OR "Circular RNA" OR "Circular RNAs" OR "long non-coding RNA" OR "long non-coding RNA" OR "lncRNA" OR "lncRNAs" OR "Small interfering RNA" OR "SiRNA" OR "Piwi-interacting RNA" OR "small nucleolar RNA" OR "ribosomal RNA" OR "transfer RNA" OR "small nuclear RNA" OR "tRNA-Derived Fragments" OR "tRNA halves" OR "miRNA" OR "circRNA" OR "tiRNA" OR "tRF" OR "miRNAs" OR "circRNAs" OR "miR*" OR "lnc*" OR "circ_*") #3 #1 AND #2 authors is not too close. A total of 15,478 authors were included among the co-cited authors in this research area, and 30 of them were cited more than 30 times in total, with Masamune Atsushi (98) having the most, followed by Anna E Szafranska (68), and David P Bartel (66). The view analysis of these 30 authors using VOSviewer software was divided into 3 clusters, as shown in Figure 4B, represented by 3 colors, Masamune, Atsushi and Minoti V Apte as the central blue cluster, Anna S Gukovskaya, Bhatia M and Banks PA as the central red cluster, Anna E Szafranska, Bartel DP, and Bloomston M were centered in the green cluster.…”

“…The latest keywords to break out in the last 2 years are injury, pathway, and extracellular vesicles, all closely related to non-coding RNAs. The topic of injury has also been mentioned in studies of acute pancreatitis, and acute pancreatitis-associated pulmonary and intestinal injuries have had a large number of correlative studies in recent years, [65][66][67] It is well illustrated that acute pancreatitis causes multi-organ functional impairment and interacts with each other. Extracellular vehicles (EVs) are generated by cells carrying proteins and nucleic acids that regulate the host immune response by mediating the transfer of intercellular substances and, therefore, play a significant role in the development and progression of inflammatory diseases, [68] and miRNAs have been extensively examined as a key component of EVs in order to investigate their roles in AP development, [69] in addition EVs have other functions that affect acute pancreatitis.…”

Ultrastructural changes of hemocapillaries of the lungs in the late development of experimental acute pancreatitis

“…The lungs are particularly susceptible to the effects of severe acute pancreatitis, with the development of ALI being a significant concern [15]. Studies have explored different interventions to mitigate the impact of acute pancreatitis on the lungs.…”