Journal ArticleDOI
c-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract.
Shigeko Torihashi,Sean M. Ward,Shin-Ichi Nishikawa,Katsuhide Nishi,Shigeru Kobayashi,Kenton M. Sanders +5 more
TLDR
Morphological experiments showed that c-kit-positive cells are ICs, and physiological evidence reinforced the concept that ICs are involved in generation of rhythmicity and translation of neural inputs in gastrointestinal smooth muscles.Abstract:
In vivo injection of a neutralizing, monoclonal antibody (ACK2) to the receptor tyrosine kinase (c-kit) disrupts the normal motility patterns of the mouse small intestine. Immunohistochemical studies showed that cells expressing c-kit-like immunoreactivity (c-kit-LI) decreased in numbers in response to ACK2, but the identity of these cells is unknown. We investigated the identity and development of the cells that express c-kit-LI in the mouse small intestine and colon. Cells in the region of the myenteric plexus and deep muscular plexus of the small intestine and in the subserosa, in the myenteric plexus region, within the circular and longitudinal muscle layers, and along the submucosal surface of the circular muscle in the colon were labeled with ACK2. The distribution of cells that express c-kit-LI was the same as that of interstitial cells (ICs). In whole-mount preparations cells with c-kit-LI were interconnected, forming a network similar to the network formed by cells that stained with methylene blue, which has been used as a marker for ICs in the mouse gastrointestinal tract. Immunocytochemistry verified that ICs were labeled with ACK2. Multiple injections of animals with ACK2 between days 0 and 8 post partum (pp) caused a dramatic reduction in the number of ICs compared to control animals. From an ultrastructural point of view, the proliferation and development appeared to be suppressed in some classes of ICs, while others displayed an altered course of development. Functional studies showed that the decrease in ICs was accompanied by a loss of electrical rhythmicity in the small intestine and reduced neural responses in the small bowel and colon. Morphological experiments showed that c-kit-positive cells are ICs, and physiological evidence reinforced the concept that ICs are involved in generation of rhythmicity and translation of neural inputs in gastrointestinal smooth muscles. Controlling the development of ICs provides a powerful new tool for the investigation of the physiological role of these cells.read more
Citations
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Journal Article
Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.
TL;DR: It is concluded that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype and it is proposed that the noncommittal name "gastrointestinal stromic tumor" be replaced by gastrointestinal pacemaker Cell tumor.
Journal ArticleDOI
The biology of stem cell factor and its receptor C-kit.
TL;DR: This review focuses on what is known about the regulation of c-Kit expression, the functions of SCF and c- Kit isoforms, and the nature of the biological responses elicited by this receptor-ligand pair with emphasis on the haemopoietic system.
Journal ArticleDOI
Interstitial cells of cajal as pacemakers in the gastrointestinal tract.
TL;DR: Slow wave frequency is regulated by a variety of physiological agonists and conditions, and shifts in pacemaker dominance can occur in response to both neural and nonneural inputs.
Journal ArticleDOI
Myofibroblasts. II. Intestinal subepithelial myofibroblasts
TL;DR: COX-2 in polyp ISEMF may be a target for nonsteroidal anti-inflammatory drugs (NSAIDs), which would account for the regression of the neoplasms in familial adenomatous polyposis and the preventive effect of NSAIDs in the development of sporadic colon neoplasm.
Journal ArticleDOI
Interstitial Cells of Cajal Mediate Cholinergic Neurotransmission from Enteric Motor Neurons
Sean M. Ward,Elizabeth A. H. Beckett,Xuan-Yu Wang,Fred Baker,Mohammad A. Khoyi,Kenton M. Sanders +5 more
TL;DR: Data suggest that IC-IM play a major role in receiving cholinergic excitatory inputs from the enteric nervous system in the murine fundus.
References
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Journal ArticleDOI
Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand.
Yosef Yarden,Wun-Jing Kuang,T. Yang-Feng,Lisa M. Coussens,S. Munemitsu,Thomas J. Dull,Ellson Y. Chen,Joseph Schlessinger,Uta Francke,Axel Ullrich +9 more
TL;DR: The results suggest that p145c‐kit functions as a cell surface receptor for an as yet unidentified ligand, and carboxy‐ and amino‐terminal truncations that occurred during the viral transduction process are likely to have generated the transformation potential of v‐kit.
Journal ArticleDOI
Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor
Krisztina M. Zsebo,David A. Williams,Edwin N. Geissler,Virginia C. Broudy,Francis Hall Martin,Harry L. Atkins,Rou Yin Hsu,Neal C. Birkett,Kenneth H. Okino,Murdock Douglas C,Frederick W. Jacobsen,Keith Langley,Kent A. Smith,Takashi Takeish,Bruce M. Cattanach,Stephen J. Galli,Sidney Vaughn Suggs +16 more
TL;DR: In vivo administration of SCF can reverse the macrocytic anemia and locally repair the mast cell deficiency of Sl/Sld mice and provide biological and physical evidence that SCF is a ligand for the c-kit receptor.
Journal ArticleDOI
The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus.
TL;DR: Observations provide the first example of a germ-line mutation in a mammalian proto-oncogene and implicate the c-kit gene as a candidate for the W locus and provide a molecular entry into this important region of the mouse genome.
Journal ArticleDOI
The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene.
TL;DR: It is shown here that the c-kit gene is disrupted in two spontaneous mutant W alleles, W44 and Wx, which strongly support the identification of c-Kit as the gene product of the W locus.
Journal ArticleDOI
The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus.
Eric J. Huang,Karl Nocka,David R. Beier,Tang-Yan Chu,Jochen Buck,Hans-Werner Lahm,Daniel Wellner,Philip Leder,Peter Besmer +8 more
TL;DR: K, a hematopoietic growth factor obtained from conditioned medium of BALB/c 3T3 fibroblasts that stimulates the proliferation of mast cells and early erythroid progenitors, specifically binds to the c-kit receptor.