Mesenchymal Stem Cell-Derived Exosomes are Effective for Radiation Enteritis and Essential for the Proliferation and Differentiation of Lgr5+ Intestinal Epithelial Stem Cells by Regulating Mir-195/Akt/ß-Catenin Pathway.
Tissue Eng Regen Med
; 20(5): 739-751, 2023 08.
Article
en En
| MEDLINE
| ID: mdl-37326937
ABSTRACT
BACKGROUND:
Radiation enteritis (RE) is a common complication of abdominal or pelvic radiotherapy, which when severe, could be life-threatening. Currently, there are no effective treatments. Studies have shown that mesenchymal stem cells (MSCs)-derived exosomes (MSC-exos) exhibit promising therapeutic effects in inflammatory diseases. However, the specific role of MSC-exos in RE and the regulatory mechanisms remain elusive.METHODS:
In vivo assay was carried out by injecting MSC-exos into the total abdominal irradiation (TAI)-induced RE mouse model. For in vitro assay, Lgr5-positive intestinal epithelial stem cells (Lgr5+ IESC) were extracted from mice, followed by irradiation along with MSC-exos treatment. HE staining was performed to measure histopathological changes. mRNA expression of inflammatory factors TNF-α and IL-6 and stem cell markers LGR5, and OCT4 were quantified by RT-qPCR. EdU and TUNEL staining was performed to estimate cell proliferation and apoptosis. MiR-195 expression in TAI mice and radiation-induced Lgr5+ IESC was tested.RESULTS:
We found that the injection of MSC-exos inhibited inflammatory reaction, increased stem cell marker expression, and maintained intestinal epithelial integrity in TAI mice. Furthermore, MSC-exos treatment increased the proliferation and simultaneously suppressed apoptosis in radiation-stimulated Lgr5+ IESC. MiR-195 expression increased by radiation exposure was decreased by MSC-exos therapy. MiR-195 overexpression facilitated the progress of RE by counteracting the effect of MSC-exos. Mechanistically, the Akt and Wnt/ß-catenin pathways inhibited by MSC-exos were activated by miR-195 upregulation.CONCLUSION:
MSC-Exos are effective in treating RE and are essential for the proliferation and differentiation of Lgr5+ IESCs. Moreover, MSC-exos mediates its function by regulating miR-195 Akt ß-catenin pathways.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Enteritis
/
Exosomas
/
Células Madre Mesenquimatosas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Tissue Eng Regen Med
Año:
2023
Tipo del documento:
Article