Epidermal growth factor primes intestinal epithelial cells for proliferative effect of insulin-like growth factor I.
Insulin-like growth factor I (IGF-I) synergistically enhances epidermal growth factor (EGF)-stimulated proliferation of intestinal epithelial cells. A possible mechanism of this synergy is that EGF acts as a "competence" factor increasing the fraction of proliferating cells by promoting transition from G0 to G1, thus allowing IGF-I, a "progression" factor, to act as a proliferative agent on the cycling population. Consistent with this hypothesis would be temporally distinct actions wherein initial brief exposure to EGF would permit synergy, whereas pretreatment with IGF-I would not. Rat intestinal epithelial cells of the IEC-18 crypt cell line were serum-deprived, then treated with EGF (5 x 10(-9) M), IGF-I (5 x 10(-9) M), or insulin (2 x 10(-6) M) for a 30-min pulse and then media containing EGF, IGF-I, insulin, or no factor was substituted for 48 hr. IGF-I and EGF each stimulated enterocyte proliferation; together they synergistically promoted cell growth. A brief pulse of IGF-I neither induced cell proliferation nor enhanced the EGF effect. Initial brief exposure to EGF, however, was equally efficacious as continuous exposure and allowed full synergy with IGF-I. Insulin at supraphysiologic levels acted similarly to IGF-I. Thus, EGF acted as a competence factor priming the cells for subsequent action by IGF-I. The cell kinetic parameters of these growth factors may be important to both physiologic and pathologic enterocyte growth regulation.
Duncan
M D
MD
Department of Surgery, VA Medical Center, Baltimore, Maryland 21201.
Korman
L Y
LY
Bass
B L
BL
D000704:Analysis of Variance; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
D016895:Culture Media, Serum-Free; D007328:Insulin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I