Gastric Mucosal Cell Cycle Regulation with Ulcer Healing by Sulglycotide

Abstract

Background: The progression of the events associated with gastric mucosal repair is controlled in an orderly manner by a plethora of the extracellular cues exerting their effect on the cell cycle regulatory proteins, cyclins, and cyclin-dependent kinases, the expression of which varies through the cycle stages. The purpose of this study was to evaluate the expression of cyclin-dependent kinase (Cdk2) and proliferating cell nuclear antigen (PCNA) during chronic ulcer healing with sulglycotide. Methods: Rats with experimentally induced gastric ulcers were treated twice daily for 14 days either with sulglycotide at 200 mg/kg or vehicle, and at different stages of the treatment their stomachs were used for macroscopic damage assessment and quantitation of gastric mucosal Cdk2 and PCNA expression. Results: The assays showed that the ulcer healing was accompanied by an increase in mucosal expression of Cdk2 and PCNA. The maximum increase in Cdk2 (2.3-fold) occurred by the 4th day of healing, whereas the expression of PCNA reached a maximum increase (4.7-fold) on the 2nd day of healing. An accelerated ulcer healing (10 days) with sulglycotide treatment was reflected in a marked enhancement in Cdk2 and PCNA. In comparison with the controls, sulglycotide caused a 2.2-fold enhancement in PCNA expression by the 2nd day of treatment and a 2.5-fold enhancement by the 6th day, whereas the Cdk2 expression attained a maximum 2.1-fold increase by the 6th day of treatment and remained substantially increased for up to 10 days. Conclusions: The findings show a complex interplay between the extracellular cues and cell cycle regulatory proteins, an orderly progression that drives the mucosal repair process. We also show that the gastroprotective agent sulglycotide is capable of affecting the expression of the cell cycle regulatory proteins that control cell cycle progression through Gl and into S phase.

Key Words:

• Cdk2
• cell cycle
• proliferating cell nuclear antigen
• sulglycotide
• ulcer healing