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Role of KIT-Positive Interstitial Cells of Cajal in the Urinary Bladder and Possible Therapeutic Target for Overactive Bladder.

Kubota Y, Kojima Y, Shibata Y, Imura M, Sasaki S, Kohri K - Adv Urol (2011)

Bottom Line: Recent research has suggested that not only the disturbance of spontaneous contractility caused by altered detrusor ICC signal transduction between nerves and smooth muscle cells but also the disturbance of signal transduction between urothelial cells and sensory nerves via suburothelial ICC may induce overactive bladder (OAB).Recent reports have suggested that KIT is not only a detection marker of these cells, but also may play a crucial role in the control of bladder function.Research into the effect of a c-kit receptor inhibitor, imatinib mesylate, on bladder function implies that KIT-positive ICCs may be therapeutic target cells to reduce bladder overactivity and that the blockage of c-kit receptor may offer a new therapeutic strategy for OAB treatment, although further study will be needed.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.

ABSTRACT
In the gastrointestinal tract, interstitial cells of Cajal (ICCs) act as pacemaker cells to generate slow wave activity. Interstitial cells that resemble ICCs in the gastrointestinal tract have been identified by their morphological characteristics in the bladder. KIT is used as an identification marker of ICCs. ICCs in the bladder may be involved in signal transmission between smooth muscle bundles, from efferent nerves to smooth muscles, and from the urothelium to afferent nerves. Recent research has suggested that not only the disturbance of spontaneous contractility caused by altered detrusor ICC signal transduction between nerves and smooth muscle cells but also the disturbance of signal transduction between urothelial cells and sensory nerves via suburothelial ICC may induce overactive bladder (OAB). Recent reports have suggested that KIT is not only a detection marker of these cells, but also may play a crucial role in the control of bladder function. Research into the effect of a c-kit receptor inhibitor, imatinib mesylate, on bladder function implies that KIT-positive ICCs may be therapeutic target cells to reduce bladder overactivity and that the blockage of c-kit receptor may offer a new therapeutic strategy for OAB treatment, although further study will be needed.

No MeSH data available.


Related in: MedlinePlus

Electron micrographs of ICC-LC in the guinea-pig bladder. ICC-LCs made close contact with nerves and each other. Arrow: ICC, arrowhead: nerves, ×4,000.
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fig2: Electron micrographs of ICC-LC in the guinea-pig bladder. ICC-LCs made close contact with nerves and each other. Arrow: ICC, arrowhead: nerves, ×4,000.

Mentions: ICCs in the bladder were also distinguishable from other cells by their unique ultrastructural features. There are several reports of ultrastructural characterization of ICC observed by transmission electron microscopy [6, 14, 23, 24]. A fundamental feature of ICCs is spindle- or stellate-shaped cells with pale eosinophilic cytoplasm and an elongated electron-dense nucleus (Figure 2). A critical element in the ultrastructure of these cells is the fibronexus, a cell-to-matrix junction, consisting of myofilament and fibronectin filament systems converging on a discrete cell-surface plaque [24]. Rasmussen et al. reported detailed information of the ultrastructure of detrusor ICCs, and revealed two different types of ICC in the human detrusor smooth muscle layer: a CD34-positive, CD-117-negative cell with a slender cytoplasmic process and myoid features, and a fibroblast-like cell. They concluded that detrusor ICCs may be analogous to ICC in the gastrointestinal tract. Wiseman et al. reported the characteristics of suburothelial ICCs [16], showing a layer of cells with the cytological characteristics of both fibroblasts and smooth muscle cells, and that ICCs included bundles of fine cytoplasmic filaments, dense bodies, linear arrays of subsurface vacuoles, and the presence of an interrupted basal lamina. These cells had close contact with unmyelinated axonal varicosities containing a mixture of clear and large dense-cored vesicles, or clear vesicles alone. Johnston et al. have also shown the ultrastructural profile of ICCs, including an absent thick filament, dense bodies or dense bands typical of smooth muscle cells, and mitochondria, ribosomes, vesicles, Golgi, and a well-developed nondilated rER [23]. These morphological studies provide a basis for future morphological and physiological investigations of ICCs under conditions of impaired bladder function.


Role of KIT-Positive Interstitial Cells of Cajal in the Urinary Bladder and Possible Therapeutic Target for Overactive Bladder.

Kubota Y, Kojima Y, Shibata Y, Imura M, Sasaki S, Kohri K - Adv Urol (2011)

Electron micrographs of ICC-LC in the guinea-pig bladder. ICC-LCs made close contact with nerves and each other. Arrow: ICC, arrowhead: nerves, ×4,000.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3139881&req=5

fig2: Electron micrographs of ICC-LC in the guinea-pig bladder. ICC-LCs made close contact with nerves and each other. Arrow: ICC, arrowhead: nerves, ×4,000.
Mentions: ICCs in the bladder were also distinguishable from other cells by their unique ultrastructural features. There are several reports of ultrastructural characterization of ICC observed by transmission electron microscopy [6, 14, 23, 24]. A fundamental feature of ICCs is spindle- or stellate-shaped cells with pale eosinophilic cytoplasm and an elongated electron-dense nucleus (Figure 2). A critical element in the ultrastructure of these cells is the fibronexus, a cell-to-matrix junction, consisting of myofilament and fibronectin filament systems converging on a discrete cell-surface plaque [24]. Rasmussen et al. reported detailed information of the ultrastructure of detrusor ICCs, and revealed two different types of ICC in the human detrusor smooth muscle layer: a CD34-positive, CD-117-negative cell with a slender cytoplasmic process and myoid features, and a fibroblast-like cell. They concluded that detrusor ICCs may be analogous to ICC in the gastrointestinal tract. Wiseman et al. reported the characteristics of suburothelial ICCs [16], showing a layer of cells with the cytological characteristics of both fibroblasts and smooth muscle cells, and that ICCs included bundles of fine cytoplasmic filaments, dense bodies, linear arrays of subsurface vacuoles, and the presence of an interrupted basal lamina. These cells had close contact with unmyelinated axonal varicosities containing a mixture of clear and large dense-cored vesicles, or clear vesicles alone. Johnston et al. have also shown the ultrastructural profile of ICCs, including an absent thick filament, dense bodies or dense bands typical of smooth muscle cells, and mitochondria, ribosomes, vesicles, Golgi, and a well-developed nondilated rER [23]. These morphological studies provide a basis for future morphological and physiological investigations of ICCs under conditions of impaired bladder function.

Bottom Line: Recent research has suggested that not only the disturbance of spontaneous contractility caused by altered detrusor ICC signal transduction between nerves and smooth muscle cells but also the disturbance of signal transduction between urothelial cells and sensory nerves via suburothelial ICC may induce overactive bladder (OAB).Recent reports have suggested that KIT is not only a detection marker of these cells, but also may play a crucial role in the control of bladder function.Research into the effect of a c-kit receptor inhibitor, imatinib mesylate, on bladder function implies that KIT-positive ICCs may be therapeutic target cells to reduce bladder overactivity and that the blockage of c-kit receptor may offer a new therapeutic strategy for OAB treatment, although further study will be needed.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.

ABSTRACT
In the gastrointestinal tract, interstitial cells of Cajal (ICCs) act as pacemaker cells to generate slow wave activity. Interstitial cells that resemble ICCs in the gastrointestinal tract have been identified by their morphological characteristics in the bladder. KIT is used as an identification marker of ICCs. ICCs in the bladder may be involved in signal transmission between smooth muscle bundles, from efferent nerves to smooth muscles, and from the urothelium to afferent nerves. Recent research has suggested that not only the disturbance of spontaneous contractility caused by altered detrusor ICC signal transduction between nerves and smooth muscle cells but also the disturbance of signal transduction between urothelial cells and sensory nerves via suburothelial ICC may induce overactive bladder (OAB). Recent reports have suggested that KIT is not only a detection marker of these cells, but also may play a crucial role in the control of bladder function. Research into the effect of a c-kit receptor inhibitor, imatinib mesylate, on bladder function implies that KIT-positive ICCs may be therapeutic target cells to reduce bladder overactivity and that the blockage of c-kit receptor may offer a new therapeutic strategy for OAB treatment, although further study will be needed.

No MeSH data available.


Related in: MedlinePlus