Plasticity of interstitial cells of cajal: a study in the small intestine of adult Guinea pigs.
Although it is well known that the reduction of interstitial cells of Cajal (ICCs) is associated with several gastrointestinal motility disorders in clinic, it is unknown whether the mature ICCs still have an active plasticity in adult mammals. This study focused on the issues of the reduction of ICCs during Imatinib administration and the recovery of ICCs following drug withdrawal in the small intestine of adult guinea pigs. ICCs were revealed by immunofluorescence on whole mount preparations with anti-Kit, alpha-smooth muscle actin, (alpha-SMA), and 5-bromo-2'-deoxyuridine (BrdU) antibodies. Moreover, the occurrence of apoptosis was also assayed. Imatinib treatment led to a gradual reduction of ICCs in number around the myenteric plexus and deep muscular plexus, which was dependent on the time but no apoptosis of ICCs was detected with the TUNEL method. During Imatinib treatment, some ICC-like cells were double labeled for Kit and alpha-SMA and a few ICC-like cells were only stained with alpha-SMA. When Imatinib was discontinued, the number of ICCs recovered to normal within 32 days. During this time, some proliferating ICCs were demonstrated by double labeling with Kit and BrdU antibodies. Our results indicated that Kit signaling was essential for the maintenance of survival and proliferation of the mature ICCs in the small intestine of adult guinea pigs. Moreover, ICCs might transdifferentiate to a type of alpha-SMA(+) cells, perhaps a phenotype of smooth muscle cells, when there is a loss-of-function of Kit.
Mei
Feng
F
Department of Histology and Embryology, Third Military Medical University, Chongqing, China.
Han
Juan
J
Huang
Yue
Y
Jiang
Zhong-Yong
ZY
Xiong
Cheng-Jie
CJ
Zhou
De-Shan
DS
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001549:Benzamides; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017615:Enteric Nervous System / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D000068877:Imatinib Mesylate; D020287:In Situ Nick-End Labeling; D007421:Intestine, Small / Q000166:cytology* / Q000294:innervation / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology
D000199:Actins; D001549:Benzamides; D000068877:Imatinib Mesylate; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D019009:Proto-Oncogene Proteins c-kit; D011743:Pyrimidines; C498862:Acta2 protein, rat