Bone Morphogenetic Protein 4 Alleviates DSS-Induced Ulcerative Colitis Through Activating Intestinal Stem Cell by...

Area of Science:

• Gastroenterology
• Stem Cell Biology
• Molecular Medicine

Background:

• Intestinal stem cell (ISC) dysfunction contributes to inflammatory bowel disease (IBD).
• Protecting ISC maintenance is a potential therapeutic strategy for IBD.

Purpose of the Study:

• To investigate the role of bone morphogenetic protein 4 (BMP4) in maintaining intestinal epithelial cell proliferation and ISC function during dextran sulfate sodium (DSS)-induced colitis.
• To explore the therapeutic potential of BMP4 in ulcerative colitis.

Main Methods:

• Utilized a DSS-induced ulcerative colitis mouse model.
• Analyzed colon epithelium and Lgr5+ ISC renewal dynamics.
• Assessed the effects of exogenous BMP4 treatment on colon mucosal damage and ISC preservation.
• Investigated the regulatory role of BMP4 on ID3 expression in colon epithelium.

Main Results:

• Colon epithelium and Lgr5+ ISCs exhibited rapid renewal in the early stages of DSS-induced colitis.
• SMAD4 and BMP4 expression were upregulated during this renewal period.
• Exogenous BMP4 treatment preserved Lgr5+ ISCs and colon epithelium turnover, reducing mucosal damage.
• BMP4 regulated ID3 expression, which was crucial for epithelium renewal and ISC maintenance.

Conclusions:

• BMP4 maintains colon epithelium cellular proliferation and ISC function through ID3 regulation in DSS-induced colitis.
• Exogenous BMP4 administration alleviates DSS-induced colitis by restoring epithelial and ISC function.
• BMP4 shows therapeutic potential for ulcerative colitis treatment.