Keratinocyte growth factor decreases total parenteral nutrition-induced apoptosis in mouse intestinal epithelium via Bcl-2

Background/Purpose: Total parenteral nutrition (TPN) induces epithelial cell (EC) apoptosis. Keratinocyte Growth Factor (KGF) increases EC-growth; however, little is known of its effect on apoptosis. This study aims to determine if mRNA expression of Bcl-2 proteins (major mediators of epithelial cell apoptosis) is altered with TPN, and if KGF-administration influences Bcl-2 family expression. Methods: C57BL/6J mice (n = 6 per group) received oral feeding (control), TPN (TPN), or TPN plus intravenous KGF daily (TPN + KGF). After 7 days, intestine was harvested and EC isolated. Apoptosis was identified using flow cytometry. EC mRNA expression of Bcl-2 family members was measured by reverse transcriptase polymerase chain reaction; Bcl-2 protein level was measured by immunoblot analysis. Results: EC apoptotic rates were: control, 14.4% +/- 5.1%; TPN, 29.4% +/- 11.3%; KGF, 17.2% +/- 5.6%. Pro-apoptotic Bcl-2 proteins changed minimally with TPN or KGF; however, the antiapoptotic protein Bcl-2 changed significantly: control, 0.78 +/- 0.24; TPN, 0.10 +/- 0.13; KGF, 0.76 +/- 0.36. EC Bcl-2 protein levels were: control, 0.16 +/- 0.13; TPN 0.18 +/- 0.16; and TPN + KGF 0.47 +/- 0.19. Conclusions: TPN-induced apoptosis decreased Bcl-2 mRNA expression. KGF decreased EC apoptosis and increased Bcl-2 expression. Modalities to increase endogenous KGF, or KGF-administration may have benefit in patients on TPN. Copyright 2003, Elsevier Science (USA). All rights reserved.