Reduction of spontaneous and irradiation-induced apoptosis in small intestine of IGF-I transgenic mice.
Insulin-like growth factor I (IGF-I) may promote survival of putative stem cells in the small intestinal epithelium. Mitosis and apoptosis were quantified in crypts of nonirradiated and irradiated IGF-I transgenic (TG) and wild-type (WT) littermates. The mean apoptotic index was significantly greater in WT vs. TG littermates. After irradiation, apoptotic indexes increased, and WT mice showed a more dramatic increase in apoptosis than TG mice at the location of putative stem cells. After irradiation, no mitotic figures were observed in WT crypts, whereas mitosis was maintained within the jejunal epithelium of TG mice. The abundance and localization of Bax mRNA did not differ between nonirradiated littermates. However, there was more Bax mRNA in TG vs. WT mice after irradiation. Bax mRNA was located along the entire length of the irradiated crypt epithelium, but there was less Bax protein observed in the bottom third of TG mouse crypts compared with WT littermates. IGF-I regulates cell number by stimulating crypt cell proliferation and decreasing apoptosis preferentially within the stem cell compartment.
Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, 27599, USA.
Heather R
HR
Wilkins
Kinuko
K
Ohneda
Temitope O
TO
Keku
A Joseph
AJ
D'Ercole
C Randall
CR
Fuller
Kristen L
KL
Williams
P Kay
PK
Lund
D000818:Animals; D017209:Apoptosis; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D007583:Jejunum / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D008940:Mitotic Index; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D007334:Insulin-Like Growth Factor I