RSPO4-CRISPR alleviates liver injury and restores gut microbiota in a rat model of liver fibrosis.
Commun Biol
; 4(1): 230, 2021 02 18.
Article
en En
| MEDLINE
| ID: mdl-33603089
ABSTRACT
Wnt signaling dysfunction and gut dysbiosis may lead to liver fibrosis, yet the underlying mechanisms are not well elucidated. This study demonstrated the role of RSPO4, a Wnt signaling agonist, in liver fibrogenesis and its impact on the gut microbiome. RSPO4 gene in CCl4-induced fibrotic-liver rats was knockout by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system, with healthy rats served as the control. Tissue samples and hepatic stellate cells (HSCs) isolated from rats were examined for curative effect of RSPO4-CRISPR treatment. Fecal sample were collected and analyzed with 16 S rRNA sequencing. We found RSPO4-CRISPR relieved liver fibrosis in rats and reversed HSC activation. Further, results showed RSPO4-CRISPR tended to restore the microflora composition. Significance species between groups were identified. Bacteroides and Escherichia-Shigella were the key microbes in the model and negative group, whereas Lactobacillus, Romboutsia, and Lachnospiraceae NK4A136 group were abundant in the control. Notably, Bacteroidales S24-7 group and Ruminococcaceae UCG-005 were the significantly enriched in CRISPR group. We show that the microbiome of rats treated with RSPO4-CRISPR presents a trend towards the restoration of the original condition. Our findings pave a new way to evaluate the curative effect of liver fibrosis treatment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_zoonosis
Asunto principal:
Terapia Genética
/
Trombospondinas
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Enfermedad Hepática Inducida por Sustancias y Drogas
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Sistemas CRISPR-Cas
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Microbioma Gastrointestinal
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Intestinos
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Hígado
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Cirrosis Hepática Experimental
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Commun Biol
Año:
2021
Tipo del documento:
Article