Dataset Information

Cathelicidin-WA Protects Against LPS-Induced Gut Damage Through Enhancing Survival and Function of Intestinal Stem Cells.

ABSTRACT: Preservation of intestinal stem cells (ISCs) plays a critical role in initiating epithelial regeneration after intestinal injury. Cathelicidin peptides have been shown to participate in regulating intestinal damage repair. However, it is not known how exactly Cathelicidin-WA (CWA) exert its function after tissue damage. Using a gut injury model in mice involving Lipopolysaccharide (LPS), we observed that CWA administration significantly improved intestinal barrier function, preserved ISCs survival, and augmented ISCs viability within the small intestine (SI) under LPS treatment. In addition, CWA administration effectively prevented proliferation stops and promoted the growth of isolated crypts. Mechanistically, our results show that the appearance of γH2AX was accompanied by weakened expression of SETDB1, a gene that has been reported to safeguard genome stability. Notably, we found that CWA significantly rescued the decreased expression of SETDB1 and reduced DNA damage after LPS treatment. Taken together, CWA could protect against LPS-induced gut damage through enhancing ISCs survival and function. Our results suggest that CWA may become an effective therapeutic regulator to treat intestinal diseases and infections.

SUBMITTER: Wang S

PROVIDER: S-EPMC8350165 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Cathelicidin-WA Protects Against LPS-Induced Gut Damage Through Enhancing Survival and Function of Intestinal Stem Cells.

Wang Sisi S Kai Lixia L Zhu Luoyi L Xu Bocheng B Chen Nana N Valencak Teresa G TG Wang Yizhen Y Shan Tizhong T

Frontiers in cell and developmental biology 20210726

Preservation of intestinal stem cells (ISCs) plays a critical role in initiating epithelial regeneration after intestinal injury. Cathelicidin peptides have been shown to participate in regulating intestinal damage repair. However, it is not known how exactly Cathelicidin-WA (CWA) exert its function after tissue damage. Using a gut injury model in mice involving Lipopolysaccharide (LPS), we observed that CWA administration significantly improved intestinal barrier function, preserved ISCs surviv ...[more]

PMID: 34381773

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Project description:Acute high-altitude hypoxia can lead to intestinal damage and changes in gut microbiota. Sustained and reliable oxygen enrichment can resist hypoxic damage at high altitude to a certain extent. However, it remains unclear whether oxygen enrichment can protect against gut damage and changes in intestinal flora caused by acute altitude hypoxia. For this study, eighteen male Sprague-Dawley rats were divided into three groups, control (NN), hypobaric hypoxic (HH), and oxygen-enriched (HO). The NN group was raised under normobaric normoxia, whereas the HH group was placed in a hypobaric hypoxic chamber simulating 7,000 m for 3 days. The HO group was exposed to oxygen-enriched air in the same hypobaric hypoxic chamber as the HH group for 12 h daily. Our findings indicate that an acute HH environment caused a fracture of the crypt structure, loss of epithelial cells, and reduction in goblet cells. Additionally, the structure and diversity of bacteria decreased in richness and evenness. The species composition at Phylum and Genus level was characterized by a higher ratio of Firmicutes and Bacteroides and an increased abundance of Lactobacillus with the abundance of Prevotellaceae_NK3B31_group decreased in the HH group. Interestingly, after oxygen enrichment intervention, the intestinal injury was significantly restrained. This was confirmed by an increase in the crypt depth, intact epithelial cell morphology, increased relative density of goblet cells, and higher evenness and richness of the gut microbiota, Bacteroidetes and Prevotellaceae as the main microbiota in the HO group. Finally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including Amino acid metabolism, energy metabolism, and metabolism. In conclusion, this study verifies, for the first time, the positive effects of oxygen enrichment on gut structure and microbiota in animals experiencing acute hypobaric hypoxia.

Dataset Information

Cathelicidin-WA Protects Against LPS-Induced Gut Damage Through Enhancing Survival and Function of Intestinal Stem Cells.

Publications

Cathelicidin-WA Protects Against LPS-Induced Gut Damage Through Enhancing Survival and Function of Intestinal Stem Cells.

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