title: Postnatal development of interstitial cells of Cajal in mouse colon in response to Kit signal blockade with Imatinib (Glivec).
abstract: 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.
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Han
authors.forename: Yin-Pin
authors.initials: YP
authors.lastname: Zhou
authors.forename: You-Zhao
authors.initials: YZ
authors.lastname: Jiang
authors.forename: Yang-Tao
authors.initials: YT
authors.lastname: He
authors.forename: Feng
authors.initials: F
authors.lastname: Mei
mesh_terms: 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
chemical_list: 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