Cathepsin G in the immune defense of the human duodenum: New sources for biosynthesis

Замолодчикова, Т. С.; Щербаков, И. Т.; Khrennikov, B. N.; Shoibonov, B. B.; Svirshchevskaya, E. V.

doi:10.1134/s0362119717020177

Cited by 5 publications

(13 citation statements)

References 18 publications

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“…A new opinion on the role of CathG is associated with the discovery of an alternative source of CathG biosynthesis in the uninflamed intestinal mucosa-specialized epithelial cells-PCs and the secretion of this enzyme in the epithelial zone, where potential CathG substrates are localized. Available data indicate a significant biosynthesis of CathG in the normal intestinal mucosa, where neutrophils are sparse (22). We focused on the potential role of the protease in the processes associated with the intestinal functioning in order to indicate the possible role of CathG in the balance between physiological and pathological conditions of the intestinal mucous membrane.…”

Section: Discussionmentioning

confidence: 99%

“…Biosynthesis of CathG in the normal mucous membrane in duodenum was identified in some types of immune cells (intraepithelial lymphocytes, lamina propria lymphocytes, CD14-positive intestinal macrophages) and in PCs-specialized epithelial cells underlying Lieberkün crypts (22). CathG in PCs was localized in the secretory granules and secretory ducts (22). Belonging to the cell type that stands at the interface of hostmicrobial interaction, PCs normally secrete antimicrobial factors such as defensins, lysozyme, phospholipase 2, immunoglobulin A (IgA), etc.…”

Section: Cathepsin G Biosynthesis In Duodenal Mucosamentioning

confidence: 99%

“…Since CathG has a capacity for protein processing, the enzyme is likely to be involved in the activation of biologically active molecules localized in the epithelial layer. CathG synthesis and secretion by PCs as well as observed sorption of the enzyme on the brush border (22) indicates the possibility of direct contact between CathG and its potential substrates, such as enteropeptidase zymogen (27) and components of the local intestinal renin-angiotensin system (RAS), expressed on the surface of the epithelium (28).…”

Section: Potential Substrates Of Cathepsin G In Intestinal Mucosamentioning

confidence: 99%

“…CathG was detected extracellularly in the small intestine of patients with Crohn's disease as a result of local neutrophil degranulation (20). Recent data indicate the presence of this protease not only in the inflamed duodenal mucosa, where CathG is localized mainly in neutrophils, but also in the normal uninflamed mucous membranes (21,22). The discovery of Paneth cells (PCs) as an alternative source of CathG biosynthesis in the duodenal mucosa indicates constitutive synthesis and secretion of the enzyme in the crypt epithelium (22).…”

Section: Introductionmentioning

confidence: 99%

“…Recent data indicate the presence of this protease not only in the inflamed duodenal mucosa, where CathG is localized mainly in neutrophils, but also in the normal uninflamed mucous membranes (21,22). The discovery of Paneth cells (PCs) as an alternative source of CathG biosynthesis in the duodenal mucosa indicates constitutive synthesis and secretion of the enzyme in the crypt epithelium (22). Using CathG as an example, we hypothesize that this immune protease can regulate not only inflammation, but may be involved also in normal physiological processes such as digestion, smooth muscle contraction, epithelial renewal, tissue remodeling, and others.…”

Section: Introductionmentioning

confidence: 99%

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Cathepsin G—Not Only Inflammation: The Immune Protease Can Regulate Normal Physiological Processes

2020

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Section: Discussionmentioning

confidence: 99%

Section: Cathepsin G Biosynthesis In Duodenal Mucosamentioning

confidence: 99%

Section: Potential Substrates Of Cathepsin G In Intestinal Mucosamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cathepsin G—Not Only Inflammation: The Immune Protease Can Regulate Normal Physiological Processes

2020

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Paneth cells: Maintaining dynamic microbiome‐host homeostasis, protecting against inflammation and cancer

et al. 2020

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The human intestines are constantly under the influence of numerous pathological factors: enteropathogenic microorganisms, food antigens, physico‐chemical stress associated with digestion and bacterial metabolism, therefore it must be provided with a system of protection against adverse impact. Recent studies have shown that Paneth cells play a crucial role in maintaining homeostasis of the small intestines. Paneth cells perform many vital functions aimed at maintaining a homeostatic balance between normal microbiota, infectious pathogens and the human body, regulate the qualitative composition and number of intestinal microorganisms, prevent the introduction of potentially pathogenic species, and protect stem cells from damage. Paneth cells take part in adaptive and protective‐inflammatory reactions. Paneth cells maintain dynamic balance between microbial populations, and the macroorganism, preventing the development of intestinal infections and cancer. They play a crucial role in gastrointestinal homeostasis and may be key factors in the etiopathological progression of intestinal diseases.

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Single-cell analysis reveals melanocytes may promote inflammation in chronic wounds through proteinase-activated receptor-2

Yakupu

Zhang

Guan

et al. 2022

Preprint

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BackgroundWound healing is a complex, highly regulated process that is critical for restoring the anatomic and functional integrity of the skin after injury, which requires the interaction of various cell types. During acute wound healing, epidermal cells will activate at precise temporal stages, and proper communication will occur between different cells and will restore the skin integrity eventually. However, why the chronic wounds stagnate in an undefined non-healing state and how the epidermal cells interact with each other in the chronic wound environment is still unclear. To provide new insights into chronic wound healing, we reconstructed the variations in the epidermal cell-cell communication network that occur in chronic wound healing via single-cell RNA-seq (scRNA-seq) data analysis. MethodsWe used the count matrix of scRNA-seq data to create a Seurat object with the R package “Seurat” which was analyzed using default parameters. GO analysis was performed for the differentially expressed genes with Enrichr by R package “Cluster Profiler”. Then we created a CellChat object with the R package “CellChat” from Seurat and reconstructed the cell-cell autocrine and paracrine signaling interactions through CellChatDB.ResultsSix cell types are annotated in each wound type and through comparing the acute and chronic wounds we found that cellular and molecular interactions of epidermal cells are enhanced in chronic wounds. Especially, the PTN and PAR signaling pathways were significantly changed in chronic wounds. Then we found the melanocyte cell population was the dominant sender of PTN and PAR signaling pathways and the most contributing ligand-receptor pairs of the PTN and PAR signaling pathways were PTN-SDC1 and CTSG-F2RL1 respectively. ConclusionsIn this study, we used CellChat to reconstruct the epidermal cell-cell autocrine and paracrine signaling networks and try to understand the underlying molecular and physiological perturbations in non-healing wounds. we speculate that melanocytes may play a key role in skin regeneration, and that the absence of the PTN pathway and increasing PAR signaling pathways may disrupt the healing in chronic wounds. In addition, we identified that CTSG and PTN may respectively be a novel potential target and a therapeutic strategy in the treatment of chronic wounds.

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Cathepsin G in the immune defense of the human duodenum: New sources for biosynthesis

Cited by 5 publications

References 18 publications

Cathepsin G—Not Only Inflammation: The Immune Protease Can Regulate Normal Physiological Processes

Cathepsin G—Not Only Inflammation: The Immune Protease Can Regulate Normal Physiological Processes

Paneth cells: Maintaining dynamic microbiome‐host homeostasis, protecting against inflammation and cancer

Single-cell analysis reveals melanocytes may promote inflammation in chronic wounds through proteinase-activated receptor-2

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