Alterations in enterocyte proliferation and apoptosis accompany TPN-induced mucosal hypoplasia and IGF-I-induced hyperplasia in rats.
The mechanisms underlying nutrient regulation of intestinal cell turnover are poorly understood. The total parenteral nutrition (TPN) model allows examination of how eliminating the growth-promoting signals stimulated by luminal nutrients, without the confounding factor of malnutrition due to food deprivation, influences enterocyte renewal. Our objective was to determine the contribution of enterocyte proliferation and apoptosis to the mucosal hypoplasia induced by TPN and the mucosal hyperplasia induced by insulin-like growth factor-I (IGF-I). We investigated the composition and structure of the jejunum and associated changes in enterocyte proliferation and apoptosis in growing rats maintained exclusively with TPN for 7 d and concurrent treatment with IGF-I or vehicle for 6 d. TPN-induced hypoplasia, specific to the small bowel mucosa, was associated with reduced enterocyte proliferation and increased apoptosis throughout the crypt and bottom half of the villus. In contrast, the hyperplastic effect of IGF-I reflected increased enterocyte proliferation and decreased apoptosis, particularly in the stem cell zone. In summary, the ability of IGF-I to prevent or reverse the decreased enterocyte proliferation and increased apoptosis accompanying TPN-induced mucosal hypoplasia substantiates the role of growth factors in tissue regeneration and emphasizes the importance of the growth-promoting signals stimulated by luminal nutrients in maintaining intestinal integrity.
Dahly
Elizabeth M
EM
Department of Nutritional Sciences, University of Wisconsin-Madison, 53706, USA.
Guo
Ziwen
Z
Ney
Denise M
DM
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001835:Body Weight; D002455:Cell Division; D020895:Enterocytes / Q000473:pathology* / Q000502:physiology*; D006965:Hyperplasia; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D007583:Jejunum / Q000378:metabolism / Q000473:pathology; D008297:Male; D008871:Microvilli / Q000502:physiology; D008938:Mitosis; D010289:Parenteral Nutrition, Total; D051381:Rats; D017207:Rats, Sprague-Dawley
D007334:Insulin-Like Growth Factor I