膀胱ICC样细胞研究进展

Cajal间质细胞(ICC)是分布在消化道自主神经末梢和平滑肌之间的一类特殊细胞,是胃肠道慢波的起搏细胞,是胃肠运动的pacemaker,它推进电活动的传播以及介导神经信号传递,控制胃肠道自主神经运动功能.近年来在人和动物膀耽中已证实存在ICC样细胞,其功能研究是最近研究的热点.ICC样细胞证实具有和胃肠ICC一样的藕联及神经调节功能的结构基础和功能特点,其是否具有起搏特性值得期待.     

Cajal间质细胞与慢性假性结肠肠梗阻关系的研究进展

Cajal间质细胞(interstitial cells of cajal,ICC)主要分布在胃肠道平滑肌细胞与神经纤维之间,是一类特殊的间质细胞,它是胃肠运动的起搏细胞,具有产生、传导慢波,调节胃肠道平滑肌运动的功能。而慢性假性肠梗阻是由于胃肠神经抑制,毒素刺激或肠壁平滑肌本身病变,导致的肠壁肌肉运动功能减弱,临床上具有肠梗阻的症状和体征,但无肠内外机械性肠梗阻因素存在,故又称动力性肠梗阻,按病程有急性和慢性之分,麻痹性肠梗阻和痉挛性肠梗阻属于急性假性肠梗阻,深入研究Cajal间质细胞,对进一步认识胃肠运动的生理及胃肠动力疾病的发生机制有重要意义。     

Caja1间质细胞与慢性假性结肠肠梗阻关系的研究进展

Cajal间质细胞（interstitial cells of cajal,ICC）主要分布在胃肠道平滑肌细胞与神经纤维之间,是一类特殊的间质细胞,它是胃肠运动的起搏细胞,具有产生、传导慢波,调节胃肠道平滑肌运动的功能。而慢性假性肠梗阻是由于胃肠神经抑制,毒素刺激或肠壁平滑肌本身病变,导致的肠壁肌肉运动功能减弱,临床上具有肠梗阻的症状和体征,但无肠内外机械性肠梗阻因素存在,故又称动力性肠梗阻。按病程有急性和慢性之分,麻痹性肠梗阻和痉挛性肠梗阻属于急性假性肠梗阻,深入研究Caja1间质细胞,对进一步认识胃肠运动的生理及胃肠动力疾病的发生机制有重要意义。     

膀胱Cajal样细胞的研究现状与展望

Cajal间质细胞(ICCs)是胃肠道的起搏者,在消化系统中具有重要的起搏功能.目前在膀胱中发现了形态学和免疫学上和ICCs相似的细胞,被称为膀胱Cajal样细胞.这类细胞既具有某些起搏细胞的特征,同时又与膀胱逼尿肌细胞紧密相连.这类细胞在膀胱活动中所起的作用就成为广大科研人员关注的问题,本文就膀胱Cajal样细胞的结构、形态、分布特点及其在信号传导中的作用进行了综述.     

新生小鼠小肠Cajal间质细胞增殖的实验研究

Cajal间质细胞（interstitial cells of Cajal,ICC）是胃肠道运动的起搏细胞,本研究拟探讨在新生小鼠小肠的发育过程中ICC是否出现增殖。采用新生2d（P2d）,14d（P14d）和24d（P24d）的小鼠小肠,采用BrdU腹腔注射,24h后取材,Kit和BrdU免疫荧光染色。Kit免疫荧光显示,Kit阳性的ICC在肌间神经丛周围呈网络状分布,     

内脏平滑肌Cajal间质细胞起搏功能(英文)

胃肠道的大部分区域都存在着一种特殊的间质细胞——Cajal间质细胞(interstitial cells of Cajal,ICCs)。尽管在100多年前它们的存在就已被发现,但是直到最近几十年的研究才逐渐揭示了它们的功能。在胃肠道,ICCs被认为是平滑肌自发性节律性电活动,即"基本电节律"(又称"慢波")的起搏细胞,并介导神经至平滑肌的神经信号传递活动。除胃肠道外,ICC样细胞同样存在于其它内脏平滑肌,如泌尿、生殖系统以及血管平滑肌等。本文仅就这些内脏平滑肌ICCs的功能做一简单综述。     

胃肠平滑肌运动单位SIP合胞体的生理与病理生理学意义

胃肠平滑肌层富有特殊分化的两种间质细胞,包括Cajal间质细胞(interstitial cells of Cajal,ICC)以及血小板衍生因子受体α阳性细胞(platelet-derived growth factor receptorα-positive cells,PDGFRα~+细胞)。ICC和PDGFRα~+细胞分别与平滑肌细胞(smooth muscle cells,SMC)形成缝隙连接调控平滑肌的收缩功能,因此,这三种细胞共同构成功能性的合胞体,称为SMC、ICC和PDGFRα~+细胞合胞体(SIP合胞体)。各种神经递质、体液因子、内源性生物活性分子以及药物等可以通过SIP合胞体影响胃肠运动。本文综述了SIP合胞体及其作用机制以及生理与病理生理学意义。     

Cajal间质细胞在急进高原胃肠动力紊乱中的作用的展望

急进高原胃肠动力紊乱是高原胃肠应激反应的主要表现之一,腹胀、恶心、呕吐、腹泻、食欲减退等是其最突出的临床症状,目前有关其的研究多集中于临床及部分基础研究上,但在探讨有关高原胃肠动力紊乱形成机制的细胞分子生物学领域的研究则少见报道。而大量研究指出,慢波起源细胞Cajal间质细胞在胃肠动力调控中具有重要作用,并成为的研究的热点,那么Cajal间质细胞是否同样在急进高原胃肠动力紊乱中发挥同样重要的作用,这不但对从细胞分子生物学角度来解释急进高原胃肠动力紊乱的机制有着重要的意义,而且还可以对未来的临床干预提供新的思路。因此,本文拟对Cajal间质细胞在急进高原胃肠动力紊乱中的潜在作用作一综述。     

嘌呤能神经-平滑肌传递过程中血小板衍生生长因子受体α阳性细胞的作用

在生理条件下,消化道的运动主要受肠神经系统(enteric nervous system, ENS)的调节。长期以来,神经系统如何将信息传递给平滑肌的机制尚不完全清楚,研究者们认为自主神经末梢在平滑肌层形成许多曲张体(varicosity),其中含有神经递质,当神经兴奋到达曲张体时,可以触发递质释放并直接扩散到平滑肌膜上,与相应受体结合引起平滑肌反应。近10年来,随着对消化道间质细胞的形态、分布特征及功能的研究进展,人们对神经信息向平滑肌传递的机制有了新的认识。目前认为,Cajal间质细胞(interstitial cell of Cajal, ICC)和血小板衍生生长因子受体α阳性(platelet-derived growth factor receptorαpositive, PDGFRα+)细胞可通过缝隙连接与平滑肌细胞形成合胞体,介导神经与平滑肌之间的信息传递。其中,嘌呤能神经递质可与PDGFRα~+细胞上的P2Y1受体结合,激活小电导钙激活钾通道(small-conductance calcium-activated potassium channel,SK3),使PDGFRα~+细胞超极化,继而这种电活动通过PDGFRα~+细胞与平滑肌之间的电耦联传递给平滑肌,引起平滑肌的超极化和舒张。本文重点综述了近10年关于嘌呤能抑制性神经如何将信息传递给消化道平滑肌的理论演变过程。     

大鼠膀胱Cajal间质细胞的分离、培养和鉴定

目的:探索大鼠膀胱Cajal间质细胞(ICC)的分离和培养方法,为进一步研究其在膀胱中的作用提供条件.方法:取大鼠的膀胱组织,采用Ⅱ型胶原酶酶解法分离细胞,将细胞悬液接种于含50ng/ml SCF、15%(v/v)FBS的DMEM培养基中,进行培养.用c-kit特异性杭体标记细胞,免疫荧光鉴定ICC细胞.结果:培养8小时后的ICC贴壁良好,并保持其固有特征:两个长的突起,多个短的侧突.胞体小,核大,c-kit抗体荧光染色阳性.结论:酶解法分离大鼠膀胱ICC并培养成功.     

Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. I. Functional development and plasticity of interstitial cells of Cajal networks

Interstitial cells of Cajal (ICC) are the pacemaker cells in gastrointestinal (GI) muscles. They also mediate or transduce inputs from enteric motor nerves to the smooth muscle syncytium. What is known about functional roles of ICC comes from developmental studies based on the discovery that ICC express c-kit. Functional development of ICC networks depends on signaling via the Kit receptor pathway. Immunohistochemical studies using Kit antibodies have expanded our knowledge about the ICC phenotype, the structure of ICC networks, the interactions of ICC with other cells within the tunica muscularis, and the loss of ICC in some motility disorders. Manipulating Kit signaling with reagents to block the receptor or downstream signaling pathways or by using mutant mice in which Kit or its ligand, stem cell factor, are defective has allowed novel studies of the development of these cells within the tunica muscularis and also allowed the study of specific functions of different classes of ICC in several regions of the GI tract. This article examines the role of ICC in GI motility, focusing on the functional development and maintenance of ICC networks in the GI tract and the phenotypic changes that can occur when the Kit signaling pathway is disrupted.     

Roles of Interleukin-9 in the Growth and Cholecystokinin-Induced Intracellular Calcium Signaling of Cultured Interstitial Cells of Cajal

Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal (GI) tract and loss of ICC is associated with many GI motility disorders. Previous studies have shown that ICC have the capacity to regenerate or restore, and several growth factors are critical to their growth, maintenance or regeneration. The present study aimed to investigate the roles of interleukin-9 (IL-9) in the growth, maintenance and pacemaker functions of cultured ICC. Here, we report that IL-9 promotes proliferation of ICC, and culturing ICC with IL-9 enhances cholecystokinin-8-induced Ca²⁺ transients, which is probably caused by facilitating maintenance of ICC functions under culture condition. We also show co-localizations of cholecystokinin-1 receptor and IL-9 receptor with c-kit by double-immunohistochemical labeling. In conclusion, IL-9 can promote ICC growth and help maintain ICC functions; IL-9 probably performs its functions via IL-9 receptors on ICC.     

Physiology and pathophysiology of the interstitial cells of Cajal: from bench to bedside. IV. Genetic and animal models of GI motility disorders caused by loss of interstitial cells of Cajal

Several human motility disorders have been shown to be associated with loss or defects in interstitial cells of Cajal (ICC) networks. Because tissue samples for these studies were taken from patients with well-advanced motility problems, it is difficult to determine whether the loss of ICC is a cause or a consequence of the disease process. To establish the cause-and-effect relationship of ICC loss in motility disorders, it may be feasible to use animal models in which ICC are lost as motility dysfunction develops. Several models with defects in ICC networks have been developed, and these include animals with defects in the Kit signaling pathway (e.g., white-spotting mutants that have defects in Kit receptors; steel mutants that have mutations in stem cell factor, the ligand for Kit; and animals that are chronically treated with reagents that block Kit or downstream signaling proteins). ICC do not die when Kit signaling is blocked, rather, they redifferentiate into a smooth muscle-like phenotype. Diabetic animals (NOD/LtJ mice), animals with chronic bowel obstruction, and inflammatory bowel models also have defects in ICC networks that have been associated with motility disorders. By studying these models with molecular and genomic techniques it may be possible to determine the signals that cause loss of ICC and find ways of restoring ICC to dysfunctional tissues. This article discusses recent progress in the utilization of animal models to study the consequences of losing ICC on the development of motility disorders.     

Expression of Ca(2+)-activated K(+) channels, SK3, in the interstitial cells of Cajal in the gastrointestinal tract

A role for small-conductance Ca²⁺-activatedK⁺ (SK) channels on spontaneous motility of thegastrointestinal tract has been suggested. Although four subtypes of SKchannels were identified in mammalian tissues, the subtypes of SKchannel expressed in the gastrointestinal tract are still unknown. Inthis study, we investigated the expression and localization of SKchannels in the gastrointestinal tract. RT-PCR analysis showsexpression of SK3 and SK4 mRNA, but not SK1 or SK2 mRNA, in the ratintestine. SK3 immunoreactivity was detected in the myenteric plexusand muscular layers of the stomach, ileum, and colon.SK3-immunoreactive cells were stained with antibody forc-kit, a marker for the interstitial cells of Cajal (ICC), but not with that for glial fibrillary acidic protein in the ileum andstomach. Immunoelectron microscopic analysis indicates that SK3channels are localized on processes of ICC that are located close tothe myenteric plexus between the longitudinal and circular musclelayers and within the muscular layers. Because ICC have been identifiedas pacemaker cells and are known to play a major role in generating theregular motility of the gastrointestinal tract, these results suggestthat SK3 channels, which are expressed specifically in ICC, play animportant role in generating a rhythmic pacemaker current in thegastrointestinal tract.

     

NPs/NPRs Signaling Pathways May Be Involved in Depression-Induced Loss of Gastric ICC by Decreasing the Production of mSCF

It is well known that natriuretic peptides (NPs) are involved in the regulation of gastrointestinal motility. Interstitial cells of Cajal (ICC) are the pacemaker cells of gastrointestinal motility and gastrointestinal dyskinesia is one of the important digestive tract symptoms of depression. However, it is unclear whether they are involved in depression-induced loss of ICC. The aim of the present study was to investigate the relationship between the natriuretic peptide signaling pathway and depression-induced loss of gastric ICC in depressed rats. These results showed that the expression of c-kit and stem cell factor (SCF) in smooth muscle layers of stomach were down-regulated in depressed rats at the mRNA and protein levels. The expression of natriuretic peptide receptor (NPR)-A, B and C were up-regulated in the stomach of depressed rats at the mRNA and protein levels. NPR-A, B and C can significantly decrease the expression of SCF to treat cultured gastric smooth muscle cells (GSMCs) obtained from normal rats with different concentrations of C-type natriuretic peptide (CNP). Pretreatment of cultured GSMCs with 8-Brom-cGMP (8-Br-cGMP, a membrane permeable cGMP analog), cANF (a specific NPR-C agonist) and CNP (10⁻⁶ mol/L) demonstrated that 8-Br-cGMP had a similar effect as CNP, but treatment with cANF did not. The results of the methyl thiazolyl tetrazolium bromide (MTT) assay indicated that high concentrations of cANF (10⁻⁶ mol/L) restrained the proliferation of cultured GSMCs. Taken together, these results indicate that the up-regulation of the NPs/NPR-C and NPs/NPR-A, B/cGMP signaling pathways may be involved in depression-induced loss of gastric ICC.     

Development of c‐kit immunopositive interstitial cells of Cajal in the human stomach

Interstitial cells of Cajal (ICC) include several types of specialized cells within the musculature of the gastrointestinal tract (GIT). Some types of ICC act as pacemakers in the GIT musculature, whereas others are implicated in the modulation of enteric neurotransmission. Kit immunohistochemistry reliably identifies the location of these cells and provides information on changes in ICC distribution and density. Human stomach specimens were obtained from 7 embryos and 28 foetuses without gastrointestinal disorders. The specimens were 7–27 weeks of gestational age, and both sexes are represented in the sample. The specimens were exposed to anti‐c‐kit antibodies to investigate ICC differentiation. Enteric plexuses were immunohistochemically examined by using anti‐neuron specific enolase and the differentiation of smooth muscle cells (SMC) was studied with anti‐α smooth muscle actin and anti‐desmin antibodies. By week 7, c‐kit‐immunopositive precursors formed a layer in the outer stomach wall around myenteric plexus elements. Between 9 and 11 weeks some of these precursors differentiated into ICC. ICC at the myenteric plexus level differentiated first, followed by those within the muscle layer: between SMC, at the circular and longitudinal layers, and within connective tissue septa enveloping muscle bundles. In the fourth month, all subtypes of c‐kit‐immunoreactivity ICC which are necessary for the generation of slow waves and their transfer to SMC have been developed. These results may help elucidate the origin of ICC and the aetiology and pathogenesis of stomach motility disorders in neonates and young children that are associated with absence or decreased number of these cells.     

Roles of interstitial cells of Cajal in regulating gastrointestinal motility: in vitro versus in vivo studies

The aim of this article is to provide a better understanding of the roles of interstitial cells of Cajal (ICC) in regulating gastrointestinal motility by reviewing in vitro and in vivo physiological motility studies. Based on the in vitro studies, ICC are proposed to have the following functions: to generate slow waves, to mediate neurotransmission between the enteric nerves and the gastrointestinal muscles and to act as mechanoreceptors. However, there is limited evidence available for these hypotheses from the in vivo motility studies. In this review, we first introduce the major subtypes of ICC and their established functions. Three Kit mutant mouse and rodent models are presented and the loss of ICC subtypes in these mutants is reviewed. The physiological motility findings from various in vitroand in vivo experiments are discussed to give a critical review on the roles of ICC in generating slow waves, regulating gastrointestinal motility, mediating neural transmission and serving as mechanoreceptors. It is concluded that the role of ICC as pacemakers may be well established, but other cells may also be involved in the generation of slow waves; the theory that ICC are mediators of neurotransmission is challenged by the majority of the in vivo motility studies; the hypothesis that ICC are mechanoreceptors has not found supportive evidence from the in vivo studies yet. More studies are needed to explain discrepancies in motility findings between the in vitro and in vivo experiments.     

Interstitial cells in the primate gastrointestinal tract

Kit immunohistochemistry and confocal reconstructions have provided detailed 3-dimensional images of ICC networks throughout the gastrointestinal (GI) tract. Morphological criteria have been used to establish that different classes of ICC exist within the GI tract and physiological studies have shown that these classes have distinct physiological roles in GI motility. Structural studies have focused predominately on rodent models and less information is available on whether similar classes of ICC exist within the GI tracts of humans or non-human primates. Using Kit immunohistochemistry and confocal imaging, we examined the 3-dimensional structure of ICC throughout the GI tract of cynomolgus monkeys. Whole or flat mounts and cryostat sections were used to examine ICC networks in the lower esophageal sphincter (LES), stomach, small intestine and colon. Anti-histamine antibodies were used to distinguish ICC from mast cells in the lamina propria. Kit labeling identified complex networks of ICC populations throughout the non-human primate GI tract that have structural characteristics similar to that described for ICC populations in rodent models. ICC-MY formed anastomosing networks in the myenteric plexus region. ICC-IM were interposed between smooth muscle cells in the stomach and colon and were concentrated within the deep muscular plexus (ICC-DMP) of the intestine. ICC-SEP were found in septal regions of the antrum that separated circular muscle bundles. Spindle-shaped histamine⁺ mast cells were found in the lamina propria throughout the GI tract. Since similar sub-populations of ICC exist within the GI tract of primates and rodents and the use of rodents to study the functional roles of different classes of ICC is warranted.