Ultrastructure of Cajal-like interstitial cells in the human detrusor

Rasmussen, Helle; Rumessen, Jüri Johannes; Hansen, Alastair; Smedts, Frank; Horn, Thomas

doi:10.1007/s00441-008-0736-z

Cited by 41 publications

(45 citation statements)

References 32 publications

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“…Immediately subjacent to the basal cells is the lamina propria containing basement membrane and connective tissue elements, blood vessels, and a diversity of cell types including fibroblasts, myofibroblasts, interstitial cells of Cajal, afferent nerve fibers, and immune cells (30,49,51,69,79,81). However, some of these cells are found within the urothelium also.…”

Section: Structure Of the Urotheliummentioning

confidence: 99%

Defining protein expression in the urothelium: a problem of more than transitional interest

Hill

2011

American Journal of Physiology-Renal Physiology

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Yu W, Hill WG. Defining protein expression in the urothelium: a problem of more than transitional interest. Am J Physiol Renal Physiol 301: F932-F942, 2011. First published August 31, 2011 doi:10.1152/ajprenal.00334.2011.-The transitional epithelium of the bladder, the urothelium, is a challenging tissue to study due to its fragility, complex cellular makeup, stratified composition, and intimate connections to both neural and connective tissue elements. With the increasing focus on the urothelium as a mechanosensory tissue with complex autocrine and paracrine signaling activities, there have arisen a number of unresolved controversies in the urothelial literature regarding whether certain important sensory and signaling proteins are expressed by the urothelium. Prominent examples of this include the transient receptor potential (TRP) family member TRPV1 and the purinergic receptor P2X 3. The problem is more than one of scientific bookkeeping since studies utilizing genetic models (primarily knockout mice) claim additional credibility for urothelial functions when phenotypes are discovered. Furthermore, both of the above-mentioned receptors are important therapeutic targets for various bladder disorders including inflammatory and neuropathic pain. The reasons for the confusion about urothelial expression are manifold, but they likely include low expression levels in some cases, poor specificity of antibodies (sometimes lacking adequate controls), the presence of nonurothelial cells resident within the urothelium, and the fact that the urothelium is particularly prone to aspecific adsorption of antibodies. In this review, we attempt to summarize some of the pitfalls with currently accepted practices in this regard, as well as to describe a set of guidelines which will improve the reliability of conclusions related to urothelial expression. It is hoped that this will be of value to investigators studying the urothelium, to those attempting to interpret conflicts in the literature, and hopefully also those charged with reviewing unpublished work. These recommendations will outline a set of "baseline" and "best practice" guidelines by which both researchers and reviewers will be able to evaluate the evidence presented.

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Section: Structure Of the Urotheliummentioning

confidence: 99%

Defining protein expression in the urothelium: a problem of more than transitional interest

Hill

2011

American Journal of Physiology-Renal Physiology

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“…The notion that KIT is expressed on IC in the bladder has been challenged in recent years by several authors [6,8,[17][18][19][20], who presented evidence that KIT in the bladder might instead be expressed by mast cells (known to be KIT + ). This has led to a lively debate on whether interspecies differences and antibody-related issues might account for the discrepant findings of KIT expression in the bladder.…”

Section: Introductionmentioning

confidence: 99%

The stem cell growth factor receptor KIT is not expressed on interstitial cells in bladder

Gevaert¹,

Vanstreels²,

Daelemans³

et al. 2017

European Urology Supplements

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The mast/stem cell growth factor receptor KIT has long been assumed to be a specific marker for interstitial cells of Cajal (ICC) in the bladder, with possible druggable perspectives. However, several authors have challenged the presence of KIT + ICC in recent years. The aim of this study was therefore to attempt to clarify the conflicting reports on KIT expression in the bladder of human beings, rat, mouse and guinea pig and to elucidate the possible role of antibody-related issues and interspecies differences in this matter. Fresh samples were obtained from human, rat, mouse and guinea pig cystectomies and processed for single/double immunohistochemistry/immunofluorescence. Specific antibodies against KIT, mast cell tryptase (MCT), anoctamin-1 (ANO1) and vimentin were used to characterize the cell types expressing KIT. Gut (jejunum) tissue was used as an external antibody control. Our results revealed KIT expression on mast cells but not on ICC in human, rat, mouse and guinea pig bladder. Parallel immunohistochemistry showed KIT expression on ICC in human, rat, mouse and guinea pig gut, which confirmed the selectivity of the KIT antibody clones. In conclusion, we have shown that KIT + cells in human, rat, mouse and guinea pig bladder are mast cells and not ICC. The present report is important as it opposes the idea that KIT + ICC are present in bladder. In this perspective, functional concepts of KIT + ICC being involved in sensory and/or motor aspects of bladder physiology should be revised.

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“…4 In the recent studies, the morphology, localization, relationships with SMCs and nerves, and possible physiological or pathological functions of ICC (in the GI tract) and kit-positive interstitial cells (ICs)/ ICC-like cells (ICC-LCs) (outside of the GI tract) have been widely investigated in various smooth muscle tissues of human and animals. [5][6][7][8] In the GI tract, ICC are considered to serve as electrical pacemakers for the generation and propagation of slow waves, and mediators of enteric motor neurotransmission, having a important role in afferent neural signaling. 6,[9][10][11] Recent morphological and functional evidence from various organs suggests that ICC and ICs might act as the primary targets for nerve-released NO to have a important role in NO-dependent signal transduction and smooth muscle relaxation.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural features and possible functional role of kit-positive interstitial cells in the guinea pig corpus cavernosum

Song

et al. 2011

Int J Impot Res

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The objective of the present study was to identify kit-positive interstitial cells (ICs) in guinea pig corpus cavernosum and examine their relationships with adjacent smooth muscle cells (SMCs) and intramural nerves. In addition, we investigated the possible involvement of ICs in nitric oxide (NO)-mediated relaxation of corpus cavernosum smooth muscle (CCSM). ICs were identified by their immunoreactivity to the kit receptor, a cell surface marker encoded by c-kit proto-oncogene and specific for interstitial cells of Cajal. ICs were abundantly distributed in guinea pig corporal tissues. Ultrastructural investigation by conventional transmission electron microscopy revealed the ultrastructural features of ICs and gap junctions located between ICs and adjacent SMCs, furthermore, a close contact between ICs and intramural nerves for the first time. Western blot analysis of purified ICs by fluorescence-activated cell sorting revealed coexpression of soluble guanylate cyclase (sGC)a1, sGCb1 and kit receptor tyrosine kinase protein in them. These observations imply that ICs express the NO-sensitive sGC molecule and may be involved in the NO-mediated relaxation of CCSM in the guinea pig corpus cavernosum.

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Ultrastructure of Cajal-like interstitial cells in the human detrusor

Cited by 41 publications

References 32 publications

Defining protein expression in the urothelium: a problem of more than transitional interest

Defining protein expression in the urothelium: a problem of more than transitional interest

The stem cell growth factor receptor KIT is not expressed on interstitial cells in bladder

Ultrastructural features and possible functional role of kit-positive interstitial cells in the guinea pig corpus cavernosum

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