Kinetics of Fibroblasts in Ulcer Healing in Rats: Interference with Indomethacin

Abstract

Objective: The authors reported that the repair of submucosal tissue is important in ulcer healing. The kinetics of fibroblasts have not been well known in gastric ulcer healing. The effect of subcutaneous administration of indomethacin (1 mg/kg) to submucosal tissue was also examined. Method: Immunohistological staining was done using the antibodies for the proliferating cell nuclear antigen prolyl 4-hydroxylase and α-smooth muscle actin in acetic acid induced gastric ulcers in rats. The terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling method was also employed. Results: The granulation tissue consisted predominantly of lymphocytes in indomethacin-treated rats. In the control group, proliferative cell nuclear antigen positive cells were at their peak 5 days after ulcer formation (day 5). Prolyl 4-hydroxylase positive fibroblasts were maximal on day 10. α-Smooth muscle actin positive myofibroblasts were few on day 5 and increased on day 15. In terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling, positive cells were sporadically seen on days 20 and 30. In indomethacin-administered rats, the fibroblasts proliferated weakly. The numbers of prolyl 4-hydroxylase and α-smooth muscle actin positive spindle-shaped cells were fewer and their appearance delayed. Nick end labeling positive cells were few before day 30 and sporadically observed on days 50 and 80. Conclusion: The results indicate that fibroblasts differentiated into several phenotypes and finally underwent apoptosis.

Both Constitutive and Inducible Prostaglandin H Synthase Affect Dermal Wound Healing in Mice

“…This again suggested the greater importance of PGHS-1 in healing during the second week after incision. Published data support the importance of prostaglandins in myofibroblast growth, because PGE 2 enhances epidermal growth factor-stimulated and fibroblast growth factor-2-stimulated proliferation of myofibroblasts in culture (Boyle et al, 1999), and indomethacin was shown to inhibit myofibroblast proliferation in the healing gastric ulcers (Hirose et al, 1997).…”

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

“…This suggests that endogenous PG and related compounds greatly contribute to gastric mucosal maintenance and prevention of mucosal injury. Hirose et al 43) examined the effects of indomethacin on fibroblast kinetics in ulcer healing in rats. In indomethacin-treated rats, fibroblasts, i.e., prolyl 4-hydroxylase and alpha-smooth muscle actinpositive spindle-shaped cells, minimally proliferated, with delayed appearance within ulcer tissue.…”

Ibuprofen inhibition of tendon cell proliferation and upregulation of the cyclin kinase inhibitor p21CIP1

“…NSAlDs have been reported to retard the proliferation and induce apoptosis in colon cancer cells and chicken embryo fibroblasts [ 1 1,231. It was postulated that indomethacin delayed the gastric ulcer healing by reducing fibroblast proliferation and inducing fibroblast apoptosis [7]. Ibuprofen at concentration of 100 pM could induce apoptosis in v-svc-transformed chicken embryo fibroblasts and this concentration is lower than those used in this study [ll].…”