Hsa-miR-375 promotes the progression of inflammatory bowel disease by upregulating TLR4.
Eur Rev Med Pharmacol Sci
; 23(17): 7543-7549, 2019 Sep.
Article
de En
| MEDLINE
| ID: mdl-31539144
ABSTRACT
OBJECTIVE:
To elucidate the biological function of hsa-miR-375 in the progression of inflammatory bowel disease (IBD) and the potential mechanism. PATIENTS ANDMETHODS:
Intestinal mucosa tissues of 26 IBD patients and 30 healthy volunteers who underwent colonoscopy were harvested for determining hsa-miR-375 level by quantitative Real-time polymerase chain reaction (qRT-PCR). Binding of hsa-miR-375 to toll-like receptor 4 (TLR4) was verified by the dual-luciferase reporter gene assay. Changes in the viability and apoptosis in Caco-2 cells influenced by hsa-miR-375 were examined by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The regulatory effect of hsa-miR-375 on the intestinal epithelial barrier was examined by detecting transepithelial electrical resistance (TEER) and lucifer yellow flux. Relative levels of TLR4, nuclear factor-kappa B (NF-κB), zonula occludens-1 (ZO-1), occludin and inflammatory factors in Caco-2 cells were detected by qRT-PCR, Western blot and enzyme-linked immunosorbent assay (ELISA).RESULTS:
Hsa-miR-375 was downregulated in intestinal mucosa tissues of patients with Crohn's disease (CD) and ulcerative colitis (UC). Knockdown of hsa-miR-375 decreased viability and TEER, but elevated apoptotic rate and lucifer yellow flux. Overexpression of hsa-miR-375 achieved the opposite trends. TLR4 was the direct downstream of hsa-miR-375, and its level was negatively mediated by hsa-miR-375. In addition, TLR4 level in Caco-2 cells was upregulated after LPS induction, while hsa-miR-375 level was unchangeable. Knockdown of hsa-miR-375 upregulated NF-κB and pro-inflammatory factors TNF-α, IL-1ß, IL-6 and IL-8, and downregulated ZO-1, occludin and anti-inflammatory factor IL-10.CONCLUSIONS:
Hsa-miR-375 is involved in the pathogenesis of IBD by upregulating TLR4 and inducing NF-κB activation.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladies inflammatoires intestinales
/
MicroARN
/
Récepteur de type Toll-4
Limites:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Eur Rev Med Pharmacol Sci
Sujet du journal:
FARMACOLOGIA
/
TOXICOLOGIA
Année:
2019
Type de document:
Article
Pays d'affiliation:
Chine