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Updated: Jan 31, 2026

Investigating Intestinal Inflammation in DSS-induced Model of IBD
Published on: February 1, 2012
SRC-3 protects intestine from DSS-induced colitis by inhibiting inflammation and promoting goblet cell
Wenbo Chen1,2, Minghui Zhuo2, Xuqiang Lu2
1Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
Abstract:
Goblet cell loss, which leads to the reduction of mucin secretion, is a hallmark of ulcerative colitis (UC). We previously reported that steroid receptor coactivator 3 (SRC-3), a transcriptional coactivator, contributes to host defense against Citrobacter rodentium by recruiting neutrophils, suggesting a role of SRC-3 in intestine homeostasis. However, the biological role of SRC-3 in UC remains unclear. Here, we showed that SRC-3-/- mice were more susceptible to dextran sulfate sodium (DSS)-induced colitis compared with wild-type mice after oral administration of 2% DSS dissolved in drinking water. After oral administration of 2% DSS, SRC-3-/- mice displayed higher mortality rate, significant body weight loss, and higher clinical symptom scores compared to wild-type mice. SRC-3-/- mice suffered a severe loss of mature colonic goblet cells, leading to more severe histopathology and more proinflammatory cytokine production. Mechanistically, SRC-3-/- mice exhibited a decreased expression of transcription factor KLF4 in the colons, which is responsible for colonic goblet cell differentiation and maturation. At the molecular level, SRC-3 cooperated with c-Fos to promote KLF4 expression at the transcriptional level. These results demonstrate that SRC-3 can ameliorate DSS-induced colitis by inhibiting inflammation and promoting colonic goblet cell differentiation and maturation through enhancing the expression of transcriptional factor KLF4, which is responsible for colonic goblet cell differentiation and maturation.
Insights
Steroid receptor coactivator 3 (SRC-3) deficiency worsens dextran sulfate sodium (DSS)-induced colitis in mice. SRC-3 promotes goblet cell differentiation and reduces inflammation by enhancing KLF4 expression, crucial for intestinal homeostasis.
Area of Science:
- Gastroenterology
- Molecular Biology
- Immunology
Background:
- Goblet cell loss and reduced mucin secretion characterize ulcerative colitis (UC).
- Steroid receptor coactivator 3 (SRC-3) plays a role in host defense and intestinal homeostasis.
- The specific role of SRC-3 in UC pathogenesis is not well understood.
Purpose of the Study:
- To investigate the biological role of SRC-3 in dextran sulfate sodium (DSS)-induced colitis, a model for UC.
- To elucidate the molecular mechanisms by which SRC-3 influences intestinal inflammation and goblet cell function.
Main Methods:
- Utilized SRC-3 knockout (SRC-3-/-) and wild-type mice in a DSS-induced colitis model.
- Administered 2% DSS in drinking water to induce colitis.
- Assessed mortality, body weight loss, clinical scores, colonic histopathology, goblet cell counts, and proinflammatory cytokine levels.
- Analyzed the expression of transcription factor KLF4 and its regulation by SRC-3 and c-Fos.
Main Results:
- SRC-3-/- mice exhibited increased susceptibility to DSS-induced colitis, with higher mortality, weight loss, and clinical scores.
- These mice showed severe loss of colonic goblet cells, exacerbated histopathology, and elevated proinflammatory cytokine production.
- SRC-3-/- mice displayed decreased colonic expression of KLF4, a key regulator of goblet cell differentiation.
- SRC-3 was found to cooperate with c-Fos to transcriptionally enhance KLF4 expression.
Conclusions:
- SRC-3 ameliorates DSS-induced colitis by inhibiting inflammation and promoting goblet cell differentiation and maturation.
- This protective effect is mediated through SRC-3's enhancement of KLF4 expression, crucial for maintaining intestinal barrier function.
- SRC-3 is a critical factor in intestinal homeostasis and warrants further investigation for UC therapeutic strategies.
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