The role of transforming growth factor beta-2, beta-3 in mediating apoptosis in the murine intestinal mucosa.
OBJECTIVE
Apoptosis is especially relevant in the gastrointestinal tract because the mammalian intestinal mucosa undergoes continual epithelial regeneration. Most recently, we confirmed the proapoptotic role of endogenous transforming growth factor (TGF)-beta in the developing chick retina as well as in chick ciliary, dorsal root, and spinal motor neurons. In the present study, we determined to establish the role of TGF-beta2 and TGF-beta3 in mediating apoptosis in non-neuronal tissue by analyzing the intestinal mucosa of Tgfbeta2(+/-) and Tgfbeta3(+/-) heterozygous mice.


METHODS
Intestinal localization of TGF-beta2 and TGF-beta3 isoforms and antiapoptotic molecules Bcl-xL and Bcl-2 was examined immunocytochemically and by Western blot analysis. Apoptosis was detected by enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and proliferation was detected by proliferating cell nuclear antigen stains.


RESULTS
TGF-beta2 was detected in endocrine cells, whereas TGF-beta3 was predominantly found in goblet cells. Programmed cell death was significantly reduced in the intestinal mucosa of Tgfbeta2(+/-) and Tgfbeta3(+/-) heterozygous mice. This decrease in apoptosis was accompanied by an increase in villus length; proliferation, however, seemed to remain unchanged. The level of Bcl-xL and Bcl-2 was significantly up-regulated in Tgfbeta2(+/-) and Tgfbeta3(+/-) mice.


CONCLUSIONS
Our data show that TGF-beta2 and TGF-beta3 play an important role in mediating apoptosis in the intestinal mucosa and regulating apoptosis-associated proteins Bcl-xL and Bcl-2 in vivo.
Dünker
Nicole
N
Anatomy and Cell Biology, University of Saarland, Homburg/Saar, Germany.
Schmitt
Kai
K
Schuster
Norbert
N
Krieglstein
Kerstin
K
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000473:pathology*; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D051020:bcl-X Protein