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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Gastrointest+Liver+Physiol
2010 ; 299
(3
): G593-601
Nephropedia Template TP
gab.com Text
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English Wikipedia
Suppression of aberrant transient receptor potential cation channel, subfamily V,
member 6 expression in hyperproliferative colonic crypts by dietary calcium
#MMPMID20508153
Peleg S
; Sellin JH
; Wang Y
; Freeman MR
; Umar S
Am J Physiol Gastrointest Liver Physiol
2010[Sep]; 299
(3
): G593-601
PMID20508153
show ga
Dietary calcium is believed to reduce colon cancer risk, but the mechanism by
which this occurs is poorly understood. Employing the Citrobacter
rodentium-induced transmissible murine colonic hyperplasia (TMCH) model, we
previously showed that a high-calcium diet (hCa) significantly abrogated
hyperplasia in the distal colons of NIH-Swiss mice. Here, we explored the
mechanism of dietary protection by hCa by analyzing the expression of genes
involved in the regulation of Ca uptake/flux in the intestinal epithelium,
including the Ca-sensing receptor, vitamin D receptor, Ca binding protein, and
transient receptor potential cation channels, subfamily V, members 5 and 6
(TRPV5/6). Interestingly, while TRPV6 expression increased significantly during
TMCH, the expression of the other gene products was unchanged. This elevated
TRPV6 expression was significantly abrogated by a hCa diet. Immunofluorescence
revealed apical membrane localization of TRPV6 in the normal colon, whereas
during TMCH we observed intense apical pole and cytoplasmic staining along the
entire longitudinal crypt axis, including the expanded proliferating zone. The
hCa diet reversed this effect. In humans, overexpression of TRPV6 was associated
with early-stage colon cancer, and in colon carcinoma cells, inhibition of TRPV6
expression by small interfering RNA inhibited their proliferation and induced
apoptosis. TRPV6 small interfering RNA also diminished the transcriptional
activity of the calcium-dependent nuclear factors in activated T cells. Thus the
aberrant overexpression of TRPV6 contributes to colonic crypt hyperplasia in mice
and to colon cancer cell proliferation in humans. Therefore, it is likely that
suppression of TRPV6 by a hCa diet is required for its protective effects in the
colon.
|Animals
[MESH]
|Calcitriol
[MESH]
|Calcium Channels/genetics/*metabolism
[MESH]
|Calcium, Dietary/*pharmacology
[MESH]
|Cell Proliferation
[MESH]
|Citrobacter rodentium
[MESH]
|Colon/cytology/metabolism/pathology
[MESH]
|Colonic Diseases/metabolism/*prevention & control
[MESH]