Keratinocyte growth factor gene therapy ameliorates ulcerative colitis in rats

Area of Science:

• Gastroenterology
• Gene Therapy
• Inflammatory Bowel Disease Research

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
• Acetic acid-induced colitis in rats serves as a relevant preclinical model for UC.
• Keratinocyte growth factor (KGF) plays a role in epithelial repair and mucosal healing.

Purpose of the Study:

• To evaluate the efficacy of KGF gene therapy delivered via attenuated Salmonella in a rat model of acetic acid-induced ulcerative colitis.
• To assess the impact of KGF gene therapy on key inflammatory and tissue repair markers.

Main Methods:

• Rats with acetic acid-induced colitis were treated orally with either a control solution, attenuated Salmonella (SP), or SP carrying the human KGF gene (SPK).
• Colonic tissues were analyzed for histological changes, KGF, KGF receptor (KGFR), and TNF-α expression.
• Biochemical markers including superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured.

Main Results:

• KGF gene therapy (SPK group) significantly improved body weight and reduced colonic inflammation compared to control and SP groups.
• SPK treatment led to increased KGF and KGFR expression, elevated Ki67, and suppressed TNF-α levels.
• Antioxidant activity (SOD) was enhanced, and oxidative stress (MDA) was reduced in the SPK-treated rats.

Conclusions:

• Attenuated Salmonella-mediated KGF gene therapy effectively ameliorates acetic acid-induced ulcerative colitis in rats.
• This therapeutic strategy demonstrates potential as a safe and effective treatment for ulcerative colitis.