ALG10 Alleviates IBD-Related Intestinal Fibrosis by Modulating the TGF-β1/PI3K/Akt Signaling Pathway

Area of Science:

• Gastroenterology
• Molecular Biology
• Fibrosis Research

Background:

• Intestinal fibrosis (IF) is a significant complication of inflammatory bowel disease (IBD).
• The molecular mechanisms driving IF progression remain incompletely understood.
• Identifying key regulators of IF is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the role of asparagine-linked glycosylation 10 (ALG10) in the pathogenesis of intestinal fibrosis.
• To elucidate the molecular mechanisms by which ALG10 influences IF.
• To explore ALG10 as a potential therapeutic target for IBD-related IF.

Main Methods:

• Utilized a TNBS/DSS-induced mouse model of intestinal fibrosis and primary colonic fibroblasts.
• Assessed pathological changes and collagen deposition using Masson's trichrome and H&E staining.
• Investigated ALG10's interaction with TGF-β1 using molecular docking, MD simulations, Co-IP, and dual-luciferase reporter assays.

Main Results:

• ALG10 expression was significantly upregulated in fibrotic intestinal tissues and cells.
• ALG10 silencing ameliorated fibrosis, reduced collagen I and α-SMA, and increased E-cadherin.
• ALG10 was found to interact with TGF-β1 and promote its promoter activity, influencing the TGF-β1/PI3K/Akt pathway.

Conclusions:

• Asparagine-linked glycosylation 10 (ALG10) plays a critical role in promoting intestinal fibrosis.
• Targeting ALG10 can alleviate IBD-related intestinal fibrosis.
• The mechanism involves the regulation of the TGF-β1/PI3K/Akt signaling pathway.