Gut Serpinome: Emerging Evidence in IBD

Mkaouar, Héla; Mariaule, Vincent; Rhimi, Soufien; Hernandez, Juan; Kriaa, Aïcha; Jablaoui, Amin; Akermi, Nizar; Maguin, Emmanuelle; Lesner, Adam; Korkmaz, Brice; Rhimi, Moez

doi:10.3390/ijms22116088

Cited by 12 publications

(13 citation statements)

References 175 publications

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“…Several human serpins have been shown to regulate serine proteases associated with processes such as inflammation and immune responses[ 48 ]. And increased activity of serine proteases is demonstrated in IBD patients and may contribute to the onset and the maintenance of the disease[ 49 ]. This appears to be a novel finding that will require additional research.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of electroacupuncture and herb-partitioned moxibustion on ulcerative colitis animal model: A study based on proteomics

Qi¹,

Zhong²,

Liu³

et al. 2022

WJG

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BACKGROUND Ulcerative colitis (UC) is a chronic, nonspecific intestinal inflammatory disease. Acupuncture and moxibustion is proved effective in treating UC, but the mechanism has not been clarified. Proteomic technology has revealed a variety of biological markers related to immunity and inflammation in UC, which provide new insights and directions for the study of mechanism of acupuncture and moxibustion treatment of UC. AIM To investigate the mechanism of electroacupuncture (EA) and herb-partitioned moxibustion (HM) on UC rats by using proteomics technology. METHODS Male Sprague-Dawley rats were randomly divided into the normal (N) group, the dextran sulfate sodium (DSS)-induced UC model (M) group, the HM group, and the EA group. UC rat model was prepared with 3% DSS, and HM and EA interventions at the bilateral Tianshu and Qihai acupoints were performed in HM or EA group. Haematoxylin and eosin staining was used for morphological evaluation of colon tissues. Isotope-labeled relative and absolute quantification (iTRAQ) and liquid chromatography-tandem mass spectrometry were performed for proteome analysis of the colon tissues, followed by bioinformatics analysis and protein-protein interaction networks establishment of differentially expressed proteins (DEPs) between groups. Then western blot was used for verification of selected DEPs. RESULTS The macroscopic colon injury scores and histopathology scores in the HM and EA groups were significantly decreased compared to the rats in the M group ( P < 0.01). Compared with the N group, a total of 202 DEPs were identified in the M group, including 111 up-regulated proteins and 91 down-regulated proteins, of which 25 and 15 proteins were reversed after HM and EA interventions, respectively. The DEPs were involved in various biological processes such as biological regulation, immune system progression and in multiple pathways including natural killer cell mediated cytotoxicity, intestinal immune network for immunoglobulin A (IgA) production, and FcγR-mediated phagocytosis. The Kyoto Encyclopedia of Genes and Genomes pathways of DEPs between HM and M groups, EA and M groups both included immune-associated and oxidative phosphorylation. Network analysis revealed that multiple pathways for the DEPs of each group were involved in protein-protein interactions, and the expression of oxidative phosphorylation pathway-related proteins, including ATP synthase subunit g (ATP5L), ATP synthase beta subunit precursor (Atp5f), cytochrome c oxidase subunit 4 isoform 1 (Cox4i1) were down-regulated after HM and EA interventions. Subsequent verification of selected DEPs (Synaptic vesicle glycoprotein 2A; nuclear cap binding protein subunit 1; carbamoyl phosphate synthetase 1; Cox4i1; ATP synthase subunit b, Atp5f1; doublecortin like kinase 3) by western blot confirmed the reliability of the iTRAQ data, HM and EA interventions can significantly down-regulat...

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Section: Discussionmentioning

confidence: 99%

Mechanism of electroacupuncture and herb-partitioned moxibustion on ulcerative colitis animal model: A study based on proteomics

Qi¹,

Zhong²,

Liu³

et al. 2022

WJG

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“…Heparin and HS enhance this tissue-protective effect; α1-protease inhibitor and members of the superfamily not only have tissue-protective roles in lung tissues but are also potent protective agents in the gut [ 143 , 146 ], and their interactions with heparin and HS further improve their protease inhibitory properties. A group of novel protease inhibitors, the siropins, are also supplied by the gut microbiome and these have tissue-protective properties [ 145 , 147 ]. A serpin from the gut bacterium Bifidobacterium longum inhibits elastase-like serine proteases [ 148 ] in a similar manner to PPS.…”

Section: Pps and The Gutmentioning

confidence: 99%

Pentosan Polysulfate Affords Pleotropic Protection to Multiple Cells and Tissues

Smith

Melrose

2023

Pharmaceuticals

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Pentosan polysulfate (PPS), a small semi-synthetic highly sulfated heparan sulfate (HS)-like molecule, shares many of the interactive properties of HS. The aim of this review was to outline the potential of PPS as an interventional therapeutic protective agent in physiological processes affecting pathological tissues. PPS is a multifunctional molecule with diverse therapeutic actions against many disease processes. PPS has been used for decades in the treatment of interstitial cystitis and painful bowel disease, it has tissue-protective properties as a protease inhibitor in cartilage, tendon and IVD, and it has been used as a cell-directive component in bioscaffolds in tissue engineering applications. PPS regulates complement activation, coagulation, fibrinolysis and thrombocytopenia, and it promotes the synthesis of hyaluronan. Nerve growth factor production in osteocytes is inhibited by PPS, reducing bone pain in osteoarthritis and rheumatoid arthritis (OA/RA). PPS also removes fatty compounds from lipid-engorged subchondral blood vessels in OA/RA cartilage, reducing joint pain. PPS regulates cytokine and inflammatory mediator production and is also an anti-tumor agent that promotes the proliferation and differentiation of mesenchymal stem cells and the development of progenitor cell lineages that have proven to be useful in strategies designed to effect repair of the degenerate intervertebral disc (IVD) and OA cartilage. PPS stimulates proteoglycan synthesis by chondrocytes in the presence or absence of interleukin (IL)-1, and stimulates hyaluronan production by synoviocytes. PPS is thus a multifunctional tissue-protective molecule of potential therapeutic application for a diverse range of disease processes.

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“…Furthermore, microbial subtilisin has been shown to promote platelet aggregation in vitro [76]; this is of interest as thrombosis and inflammation are also connected in IBD [77]. The role of antisubtilisin inhibitors may thus have some therapeutic potential in this respect [78]. Antimicrobial effects of PIs have been studied to some extent, also regarding some gut health-related species [79].…”

Section: Impact On Gut Microbiota Population and Metabolic Dynamicsmentioning

confidence: 99%

Intestinal Exposure to Food-Derived Protease Inhibitors: Digestion Physiology- and Gut Health-Related Effects

et al. 2021

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Plant-derived protease inhibitors (PI), such as Bowman-Birk inhibitors and Kunitz-type inhibitors, have been suggested to negatively affect dietary protein digestion by blocking the activity of trypsin and chymotrypsin in the human gastrointestinal system. In addition, some PIs may possess proinflammatory activities. However, there is also scientific evidence on some beneficial effects of PIs, for example, gut-related anti-inflammatory and chemopreventive activities in vitro and in vivo. Some PIs are sensitive to processing and digestion; thus, their survival is an important aspect when considering their positive and negative bioactivities. The aim of this review was to evaluate the relevance of PIs in protein digestion in humans and to discuss the potential of PIs from whole foods and as purified compounds in decreasing symptoms of bowel-related conditions. Based on the reviewed literature, we concluded that while the complex interactions affecting plant protein digestibility and bioavailability remain unclear, PI supplements could be considered for targeted purposes to mitigate inflammation and gastric pain.

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Gut Serpinome: Emerging Evidence in IBD

Cited by 12 publications

References 175 publications

Mechanism of electroacupuncture and herb-partitioned moxibustion on ulcerative colitis animal model: A study based on proteomics

Mechanism of electroacupuncture and herb-partitioned moxibustion on ulcerative colitis animal model: A study based on proteomics

Pentosan Polysulfate Affords Pleotropic Protection to Multiple Cells and Tissues

Intestinal Exposure to Food-Derived Protease Inhibitors: Digestion Physiology- and Gut Health-Related Effects

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