Kinetics of fibroblasts in ulcer healing in rats: interference with indomethacin.
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.


METHODS
Immunohistological staining was done using the antibodies for the proliferating cell nuclear antigen prolyl 4-hydroxylase and alpha-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. Alpha-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 alpha-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.


CONCLUSIONS
The results indicate that fibroblasts differentiated into several phenotypes and finally underwent apoptosis.
Hirose
Y
Y
2nd Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Goto
H
H
Arisawa
T
T
Hase
S
S
Niwa
Y
Y
Hayakawa
T
T
Asai
J
J
Tsukamoto
Y
Y
D019342:Acetic Acid; D000199:Actins / Q000032:analysis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D046508:Culture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010641:Phenotype; D011393:Procollagen-Proline Dioxygenase / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D014945:Wound Healing / Q000187:drug effects*
D000199:Actins; D016861:Cyclooxygenase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D011393:Procollagen-Proline Dioxygenase; D019342:Acetic Acid; D007213:Indomethacin