Postnatal development of interstitial cells of Cajal in mouse colon in response to Kit signal blockade with Imatinib (Glivec).
This study investigated the response of interstitial cells of Cajal (ICC) in postnatal mouse colon to treatment with Imatinib (Glivec), a potent inhibitor of Kit receptor). ICC were revealed by immunofluorescent staining on frozen cross-sections and whole-mount preparations by anti-Kit and DOG1 antibodies. Kit and p-Kit protein were also evaluated by Western blot. After administration of Imatinib for 4 days beginning at 8 days post-partum (P8), the mean density of Kit+ ICC, which were localized around the myenteric nerve plexus (ICC-MY), within smooth muscle layers (ICC-IM) and in the connective tissue beneath the serosa (ICC-SS), was dramatically decreased to about 50% when compared with controls, but those Kit+ cells located at the submucosal border of circular smooth muscle layer (ICC-SM) seemed to be unchanged in both cell number and morphology. A small number of DOG1+/Kit(-) cells appeared during Imatinib administration. However, these Kit+ ICC were not changed in mice even after 12 days of Imatinib treatment from P24. When Imatinib was discontinued, the number of ICC recovered to normal within 4 days. Our results indicate that the postnatal development of ICC in the mouse colon is Kit dependent, but ICC-SM are unlikely, and the Kit dependence of ICC development is also age-dependent.
Han
Juan
J
Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China.
Zhou
Yin-Pin
YP
Jiang
You-Zhao
YZ
He
Yang-Tao
YT
Mei
Feng
F
D000367:Age Factors; D000818:Animals; D000075369:Anoctamin-1; D000906:Antibodies / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D002454:Cell Differentiation; D049109:Cell Proliferation; D018118:Chloride Channels / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000166:cytology* / Q000254:growth & development; D003238:Connective Tissue / Q000378:metabolism; D000068877:Imatinib Mesylate; D056885:Interstitial Cells of Cajal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D009197:Myenteric Plexus / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity; D010879:Piperazines / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D012704:Serous Membrane / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D000906:Antibodies; D000970:Antineoplastic Agents; D001549:Benzamides; D018118:Chloride Channels; D008565:Membrane Proteins; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit