Activation of p38 MAPK and expression of TGF-beta 1 in rat colon enterocytes after whole body gamma-irradiation
Abstract
Purpose : To examine the p38 mitogen-activated protein kinase (p38) phosphorylation and transforming growth factor beta 1 (TGF-beta 1) expression in rat colon enterocytes after irradiation and their contribution to pathology of intestinal radiation disease. Materials and methods : Male Wistar rats were irradiated with whole body gamma-radiation of 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 Gy (Co-60, 1.44 Gy.min(-1)).
Samples were taken 4 and 24 h after irradiation, immunohistochemically stained, then p38 phosphorylation and TGF-beta 1 expression were measured in apical and cryptal enterocytes using computer image analysis. In selected groups, morphometric parameters, mitosis and apoptosis were evaluated.
Results : P38 phosphorylation integrated optical density (IOD)-based levels increased 2.4-fold (p <= 0.01) and 3.6 to 22.8-fold (p <= 0.001) in apical enterocytes 4 h after 0.5 Gy and 24 h after 3-10 Gy, respectively. TGF-beta 1 IOD-based expression increased 3.3- to 6.9-fold (p <= 0.001) and 1.6- to 4.9-fold (p <= 0.001) in apical cells 4 h after 0.5-2, 4, 5 Gy and 24 h after 6-10 Gy, respectively.
No changes were observed in crypts. Conclusions : We found a chronological and dose-dependent order of p38 activation and TGF-beta 1 expression in apical enterocytes.
Transient up-regulation of p38 and TGF-beta 1 signalling observed 4 h after low-dose irradiation may participate in molecular mechanisms creating cellular over-expression in apical compartment, while persistent patterns measured 24 h after high-dose irradiation might provide protection of remaining cells in order to maintain tissue integrity.