The lncRNAs UCA1 and CRNDE target miR-145/TLR4/NF-қB/TNF-α axis in acetic acid-induced ulcerative colitis model: The beneficial role of 3,3-Diindolylmethane.

Autor: El-Boghdady NA; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt., El-Hakk SA; Pharmacist, General Assuit Hospital, Assuit, Egypt., Abd-Elmawla MA; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: mei.abdelmawla@pharma.cu.edu.eg.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2023 Aug; Vol. 121, pp. 110541. Date of Electronic Publication: 2023 Jun 28.
DOI: 10.1016/j.intimp.2023.110541
Abstrakt: Introduction: Ulcerative colitis (UC) is a chronic disease that alters the colonic and rectal mucosa. The high prevalence rates of UC make it a worldwide healthcare problem. However, its underlying molecular mechanisms remain vague.
Aim of the Study: To investigate the molecular mechanisms underlying UC and to study the cross-talk among the regulatory role of the lncRNAs UCA1, CRNDE, and miR-145 on TLR4/NF-κB/TNF-α signaling pathway. Moreover, the study was extended to examine the beneficial effects of 3,3-Diindolylmethane (DIM) on relieving UC.
Methods: UC was induced in rats by injecting 2 ml of 4% acetic acid (AA) solution transrectally. After 24 h, rats were treated with either DIM (20 mg/kg) or sulphasalazine (SSZ) (500 mg/kg) orally for 7 days.
Results: The present study revealed that the gene expression of the lncRNAs UCA1 and CRNDE were significantly upregulated in the AA-induced UC model compared with the control group, whereas miR-145 was significantly downregulated. There was a significant association between the expression of these non-coding RNAs and TLR4/ NF-κB/TNF-α axis as well as malondialdehyde and glutathione levels. Favorably, the DIM-treated group showed significant downregulation of the lncRNAs UCA1 and CRNDE along with upregulated miR-145 compared with the AA-induced UC model. Furthermore, DIM showed remarkable inhibition of the TLR4/ NF-κB /TNF-α cascade compared with non-treated UC rats.
Conclusions: The present study is the first to document the interrelated role of the lncRNAs UCA1 and CRNDE in UC via orchestrating miR-145/TLR4/ NF-κB /TNF-α inflammatory cascade. Furthermore, the study demonstrated a new molecular basis for the pleiotropic activities of DIM in relieving UC.
Competing Interests: Declaration of Competing Interest The authors declare that they haven't any competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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