Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by transforming growth factor beta and angiotensin II.
BACKGROUND
Absorption of water and Na+ in descending colonic crypts is dependent on the barrier function of the surrounding myofibroblastic pericryptal sheath. Here the effects of high and low Na+ diets and exposure to whole body ionising radiation on the growth and activation of the descending colonic pericryptal myofibroblasts are evaluated. In addition the effect of a post-irradiation treatment with the angiotensin converting enzyme inhibitor Captopril was investigated.


METHODS
The levels of Angiotensin II type 1 receptor (AT1), ACE, collagen type IV, transforming growth factor-beta type 1 receptor (TGF-betaR1), OB cadherin and alpha-smooth muscle actin in both descending colon and caecum were evaluated, using immunocytochemistry and confocal microscopy, in rats fed on high and low Na+ diets (LS). These parameters were also determined during 3 months post-irradiation with 8Gy from a 60Co source in the presence and absence of the angiotensin converting enzyme inhibitor, Captopril.


RESULTS
Increases in AT1 receptor (135.6% +/- 18.3, P < 0.001); ACE (70.1% +/- 13.1, P < 0.001); collagen type IV (49.6% +/- 15.3, P < 0.001); TGF-+/-beta1 receptors (291.0% +/- 26.5, P < 0.001); OB-cadherin (26.3% +/- 13.8, P < 0.05) and alpha-smooth muscle actin (82.5% +/- 12.4, P < 0.001) were observed in the pericryptal myofibroblasts of the descending colon after LS diet. There are also increases in AT1 receptor and TGF-beta1 receptor, smooth muscle actin and collagen type IV after irradiation. Captopril reduced all these effects of irradiation on the pericryptal sheath and also decreased the amount of collagen and smooth muscle actin in control rats (P < 0.001).


CONCLUSIONS
These results demonstrate an activation of descending colonic myofibroblasts to trophic stimuli, or irradiation, which can be attenuated by Captopril, indicative of local trophic control by angiotensin II and TGF-beta release.
Thiagarajah
Jay R
JR
Division of Physiology, School of Biomedical Sciences, King's College London, Guys Campus, London, UK. jaythiagarajah@hotmail.com
Griffiths
Nina M
NM
Pedley
Kevin C
KC
Naftalin
Richard J
RJ
D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004039:Diet, Sodium-Restricted; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D005355:Fibrosis; D008297:Male; D011832:Radiation Injuries / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012982:Sodium, Dietary / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000502:physiology*
D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D012982:Sodium, Dietary; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D003094:Collagen; D002216:Captopril