Effect of glucocorticoid on expression of rat MUC5AC mRNA in rat gastric mucosa in vivo and in vitro.
The gastric mucus is an important factor in the gastric mucosal protection from acid, pepsin and various reagents (alcohol, aspirin, etc.). MUC5AC is the mucin secreted from surface mucous cells, and belongs to the gel-forming mucin. We examined the regulation of rat MUC5AC (rMUC5AC) mRNA by glucocorticoid in vivo and in vitro, comparing it with that of pepsinogen (Pg) mRNA. By adrenal gland resection, rMUC5AC and Pg mRNA levels and Pg content in rats significantly decreased to 70%, 46% and 42% of those in the sham operated controls, respectively. With the treatment of hydrocortisone (1, 5 and 50 mg/kg), Pg mRNA level and Pg content in adrenalectomized rats was restored. On the other hand, the rMUC5AC mRNA level exceeded the control with 1 or 5 mg/kg injections of hydrocortisone, but drastically decreased to 18% of sham operation levels with it (50 mg/kg). Similar results were obtained in normal rats with the treatment of hydrocortisone (50 mg/kg). Mucus and DNA content of cultured rat gastric epithelial cells were not affected by hydrocortisone, but rMUC5AC mRNA level was significantly decreased in a dose-dependent manner. From the in vivo and in vitro results, at least a physiological concentration of glucocorticoid was necessary in the expression of rMUC5AC mRNA. However, high dose of hydrocortisone directly suppressed the expression of rMUC5AC mRNA. These results suggested that hydrocortisone might directly cause the suppression and indirectly the enhancement of the mucin biosynthesis.
Tanaka
T
T
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
Kobayashi
T
T
Sunaga
K
K
Tani
S
S
D000315:Adrenalectomy; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D017931:DNA Primers; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D055271:Mucin 5AC; D009077:Mucins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar
D017931:DNA Primers; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger; D004247:DNA; D006854:Hydrocortisone