Acupuncture protects the interstitial cells of Cajal by regulating miR-222 in a rat model of post-operative ileus

2019 ◽  
Vol 37 (2) ◽  
pp. 125-132 ◽  
Author(s):  
Jing-jing Deng ◽  
Ming-yin Lai ◽  
Xinghua Tan ◽  
Qing Yuan
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Enos Mrna ◽  
Underlying Mechanisms ◽  
Cells Of Cajal ◽  
Endothelial Nitric Oxide ◽  
Gi Motility

Background: Recovery of the interstitial cells of Cajal (ICCs) during post-operative ileus (POI) is important for the restoration of gastrointestinal (GI) motility. Acupuncture can protect ICCs, but the underlying mechanisms remain unclear. In this study, we investigated whether miR-222, c-kit and endothelial nitric oxide synthase (eNOS) are involved in the putative effects of acupuncture on ICC recovery. Methods: A POI model was established in Sprague-Dawley rats by colo-colic anastomosis, and then acupuncture was performed at bilateral ST36, SP6 and LR3 once daily for 3 consecutive days. C-kit protein expression in the colonic tissue adjacent to the incision site was determined by immunohistochemistry and Western blotting. mRNA levels of c-kit, eNOS and miR-222 were measured by real-time polymerase chain reaction (RT-PCR). Results: The levels of c-kit mRNA/protein and eNOS mRNA decreased, while miR-222 increased in the colonic tissues of POI model rats. Acupuncture treatment improved GI motility, inhibited the up-regulation of miR-222 and blocked the down-regulation of c-kit mRNA/protein and eNOS mRNA. The levels of miR-222 and c-kit were negatively correlated. Conclusion: Acupuncture at ST36, SP6 and LR3 facilitates ICC recovery and improves post-operative GI motility in part through regulation of miR-222, c-kit and eNOS.

scholarly journals Electroacupuncture at Zusanli (ST36) Repairs Interstitial Cells of Cajal and Upregulates c-Kit Expression in Rats with SCI-Induced Neurogenic Bowel Dysfunction

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yujie Yang ◽  
Jie Cheng ◽  
Yongni Zhang ◽  
Jiabao Guo ◽  
Bin Xie ◽  
...  
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Bowel Dysfunction ◽  
Interstitial Cells ◽  
Colonic Transit ◽  
Sprague Dawley ◽  
Ultrastructural Morphology ◽  
Sprague Dawley Rats ◽  
Cord Injury ◽  
Cells Of Cajal ◽  
Neurogenic Bowel

Background. Electroacupuncture (EA) could improve colonic transit activity in rats with neurogenic bowel dysfunction (NBD) caused by spinal cord injury (SCI). The function of interstitial cells of Cajal (ICCs) and c-Kit expression may play essential roles in this process. Material and Methods. Thirty-six Sprague Dawley rats were randomized to the sham group, the SCI group, or the SCI + EA group (bilateral Zusanli, 30 min/day, 14 days). Changes in the ultrastructural morphology of ICCs were observed. The c-Kit expression on different levels was analyzed by immunohistochemistry, Western blotting, and RT-qPCR, respectively. Results. Abnormal morphology of ICCs and downregulation of the c-Kit expression occurred after SCI. While the number of ICCs was increased, the ultrastructural morphology was improved significantly in EA rats. They also showed better improvement in c-Kit expression at both protein and gene levels. Conclusion. Abnormal ICCs in colon tissues and the downregulated expression of c-Kit could be observed after SCI. EA at Zusanli (ST36) could improve the colon function by repairing the morphology and increasing the number of ICCs and upregulating c-Kit expression.

scholarly journals Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials Through M2 and M3 Muscarinic Receptors in Cultured Murine Small Intestine Interstitial Cells of Cajal

2017 ◽  
Vol 43 (5) ◽  
pp. 1790-1802 ◽  
Author(s):  
Hyun Jung Kim ◽  
Taewon Han ◽  
Yun Tai Kim ◽  
Insuk So ◽  
Byung Joo Kim
Keyword(s):  
Receptor Antagonist ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Potential ◽  
Pacemaker Potentials ◽  
Magnolia Officinalis ◽  
Cells Of Cajal ◽  
Gi Motility

Background: Magnolia officinalis Rehder and EH Wilson (M. officinalis) are traditional Chinese medicines widely used for gastrointestinal (GI) tract motility disorder in Asian countries. We investigated the effects of an ethanol extract of M. officinalis (MOE) on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) in vitro and its effects on GI motor functions in vivo. Methods: We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs in vitro. Both gastric emptying (GE) and intestinal transit rates (ITRs) were investigated in normal and GI motility dysfunction (GMD) mice models in vivo. Results: MOE depolarized ICC pacemaker potentials dose-dependently. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) and 4-DAMP (a muscarinic M3 receptor antagonist) inhibited the effects of MOE on the pacemaker potential relative to treatment with MOE alone. In addition, MOE depolarized pacemaker potentials after pretreatment with Y25130 (a 5-HT3 receptor antagonist), GR113808 (a 5-HT4 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca2+ free solution or thapsigargin. In normal mice, the GE and ITR values were significantly and dose-dependently increased by MOE. In loperamide-and cisplatin-induced GE delay models, MOE administration reversed the GE deficits. The ITRs of the GMD mice were significantly reduced relative to those of normal mice, which were significantly and dose-dependently reversed by MOE. Conclusion: These results suggest that MOE dose-dependently depolarizes ICCs pacemaker potentials through M2 and M3 receptors via internal and external Ca2+ regulation through G protein pathways in vitro. Moreover, MOE increased GE and ITRs in vivo in normal and GMD mouse models. Taken together, the results of this study show that MOE have the potential for development as a gastroprokinetic agent in GI motility function.

scholarly journals Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis

2018 ◽  
Vol 47 (2) ◽  
pp. 535-544 ◽  
Author(s):  
Zhen-peng Huang ◽  
Hu Qiu ◽  
Bao-ping Yu
Keyword(s):  
Acute Cholecystitis ◽  
Guinea Pigs ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Motility Disorder ◽  
Gallbladder Motility ◽  
Control Group ◽  
Mrna Levels ◽  
Duct Ligation ◽  
Cells Of Cajal

Background/Aims: Acute cholecystitis is a common gastrointestinal disorder, often characterized by acute cholecystitis with gallbladder motility disorder. Interstitial cells of Cajal (ICCs) are the pacemaker cells of gut motility in the gastrointestinal tract. Disruption of ICC function is related to motility disorders. The aim of this study was to explore the cellular and molecular mechanisms of ICCs in acute cholecystitis and after the resolution of acute inflammation. Materials and Methods: Fifty adult guinea pigs were randomly divided into five groups: a sham-administered group (control group); two groups that were intraperitoneally administered an anti-polyclonal neutrophil (PMN) antibody 24 h before common bile duct ligation (CBDL); and two groups of guinea pigs that were subjected to CBDL without receiving the PMN antibody. Guinea pigs that underwent CBDL were held for 24 h or 48 h after surgery before being subjected to laparotomy and cholecystectomy. Immunohistochemistry, TUNEL assays, western blotting, and real-time PCR were performed to determine ICC morphology and density, to detect ICC apoptosis, and to examine stem cell factor (SCF) and c-kit protein expression and SCF and c-kit mRNA levels, respectively. Results: Both hematoxylin-eosin staining and histological inflammation scores in the PMN groups were lower than those in the control groups (P < 0.01). No differences were observed in ICC morphology between groups. During acute cholecystitis, ICCs numbers were reduced. Conversely, the density of ICCs increased after inflammation was relieved (P < 0.01). In addition, SCF and c-kit protein and mRNA expression levels decreased during acute cholecystitis (P < 0.05) and increased after inflammation was relieved (P < 0.05). Furthermore, ICC apoptosis increased during acute cholecystitis and decreased after resolution of acute cholecystitis (P < 0.01). Conclusions: In acute cholecystitis, ICC injury may be related to gallbladder motility disorder.

scholarly journals Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius

2001 ◽  
Vol 91 (3) ◽  
pp. 1091-1098 ◽  
Author(s):  
Christopher R. Woodman ◽  
William G. Schrage ◽  
James W. E. Rush ◽  
Chester A. Ray ◽  
Elmer M. Price ◽  
...  
Keyword(s):  
Blood Flow ◽  
Protein Content ◽  
Sprague Dawley ◽  
Enos Expression ◽  
Hindlimb Unweighting ◽  
Sprague Dawley Rats ◽  
Mrna Content ◽  
Enos Mrna ◽  
Endothelial Nitric Oxide

We tested the hypothesis that hindlimb unweighting (HLU) decreases endothelium-dependent vasodilation and expression of endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) in arteries of skeletal muscle with reduced blood flow during HLU. Sprague-Dawley rats (300–350 g) were exposed to HLU ( n = 15) or control ( n = 15) conditions for 14 days. ACh-induced dilation was assessed in muscle with reduced [soleus (Sol)] or unchanged [gastrocnemius (Gast)] blood flow during HLU. eNOS and SOD-1 expression were measured in feed arteries (FA) and in first-order (1A), second-order (2A), and third-order (3A) arterioles. Dilation to infusion of ACh in vivo was blunted in Sol but not Gast. In arteries of Sol muscle, HLU decreased eNOS mRNA and protein content. eNOS mRNA content was significantly less in Sol FA (35%), 1A arterioles (25%) and 2A arterioles (18%). eNOS protein content was less in Sol FA (64%) and 1A arterioles (65%) from HLU rats. In arteries of Gast, HLU did not decrease eNOS mRNA or protein. SOD-1 mRNA expression was less in Sol 2A arterioles (31%) and 3A arterioles (29%) of HLU rats. SOD-1 protein content was less in Sol FA (67%) but not arterioles. SOD-1 mRNA and protein content were not decreased in arteries from Gast. These data indicate that HLU decreases endothelium-dependent vasodilation, eNOS expression, and SOD-1 expression primarily in arteries of Sol muscle where blood flow is reduced during HLU.

IV. Pathophysiology of GI motility related to interstitial cells of Cajal

1998 ◽  
Vol 275 (3) ◽  
pp. G381-G386 ◽  
Author(s):  
Jan D. Huizinga
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Intrinsic Properties ◽  
Peristaltic Activity ◽  
Rapid Pace ◽  
Delayed Maturation ◽  
Motor Abnormalities ◽  
Cells Of Cajal ◽  
Important Evidence ◽  
Gi Motility

Our understanding of the physiological roles played by interstitial cells of Cajal (ICC) in relation to gastrointestinal (GI) motility is still rudimentary. Nevertheless, studies into the pathophysiology of ICC are emerging at a rapid pace. Caution should be exercised, however, in assuming correlations between changes in Kit immunoreactivity, findings of ultrastructural abnormalities in ICC, and the pathophysiology and symptoms of the patients. Recent studies have revealed reduced numbers or the absence of ICC in small intestine and colon that do not exhibit normal peristaltic activity. Furthermore, important evidence is emerging that motor abnormalities in newborns may be associated with delayed maturation of the ICC network. These preliminary clinical studies provide plausible hypotheses toward the pathophysiology of certain motor disorders and strongly encourage basic scientific studies directed toward discovering the intrinsic properties of ICC as well as obtaining a deeper understanding of the physiological roles played by these cells.

EDHF contributes to strain-related differences in pulmonary arterial relaxation in rats

2001 ◽  
Vol 280 (3) ◽  
pp. L458-L464 ◽  
Author(s):  
M. R. Karamsetty ◽  
J. M. Nakashima ◽  
L.-C. Ou ◽  
J. R. Klinger ◽  
N. S. Hill
Keyword(s):  
Pulmonary Arteries ◽  
Relaxation Response ◽  
Sprague Dawley ◽  
Protein Levels ◽  
Sprague Dawley Rats ◽  
Enos Mrna ◽  
Pulmonary Arterial ◽  
Relaxation Responses ◽  
And Function ◽  
Endothelial Nitric Oxide

Pulmonary arteries from the Madison (M) strain relax more in response to acetylcholine (ACh) than those from the Hilltop (H) strain of Sprague-Dawley rats. We hypothesized that differences in endothelial nitric oxide (NO) synthase (eNOS) expression and function, metabolism of ACh by cholinesterases, release of prostacyclin, or endothelium-derived hyperpolarizing factor(s) (EDHF) from the endothelium would explain the differences in the relaxation response to ACh in isolated pulmonary arteries. eNOS mRNA and protein levels as well as the NO-dependent relaxation responses to thapsigargin in phenylephrine (10−6 M)-precontracted pulmonary arteries from the M and H strains were identical. The greater relaxation response to ACh in M compared with H rats was also observed with carbachol, a cholinesterase-resistant analog of ACh, a response that was not modified by pretreatment with meclofenamate (10−5M). N ω-nitro-l-arginine (10−4 M) completely abolished carbachol-induced relaxation in H rat pulmonary arteries but not in M rat pulmonary arteries. Precontraction with KCl (20 mM) blunted the relaxation response to carbachol in M rat pulmonary arteries and eliminated differences between the M and H rat pulmonary arteries. NO-independent relaxation present in the M rat pulmonary arteries was significantly reduced by 17-octadecynoic acid (2 μM) and was completely abolished by charybdotoxin plus apamin (100 nM each). These findings suggest that EDHF, but not NO, contributes to the strain-related differences in pulmonary artery reactivity. Also, EDHF may be a metabolite of cytochrome P-450 that activates Ca2+-dependent K+ channels.

scholarly journals Understanding the Biology of Human Interstitial Cells of Cajal in Gastrointestinal Motility

2020 ◽  
Vol 21 (12) ◽  
pp. 4540 ◽  
Author(s):  
Daphne Foong ◽  
Jerry Zhou ◽  
Ali Zarrouk ◽  
Vincent Ho ◽  
Michael D. O’Connor
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Clinical Care ◽  
Cell Types ◽  
Interstitial Cells ◽  
Enteric Neurons ◽  
Motility Disorders ◽  
Fundamental Causes ◽  
Chronic Nausea ◽  
Cells Of Cajal ◽  
Gi Motility

Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such as chronic nausea and vomiting. As no cures are currently available, clinical care is limited to symptom management, while the underlying causes of impaired GI motility remain unaddressed. The efficient movement of contents through the GI tract is facilitated by peristalsis. These rhythmic slow waves of GI muscle contraction are mediated by several cell types, including smooth muscle cells, enteric neurons, telocytes, and specialised gut pacemaker cells called interstitial cells of Cajal (ICC). As ICC dysfunction or loss has been implicated in several GI motility disorders, ICC represent a potentially valuable therapeutic target. Due to their availability, murine ICC have been extensively studied at the molecular level using both normal and diseased GI tissue. In contrast, relatively little is known about the biology of human ICC or their involvement in GI disease pathogenesis. Here, we demonstrate human gastric tissue as a source of primary human cells with ICC phenotype. Further characterisation of these cells will provide new insights into human GI biology, with the potential for developing novel therapies to address the fundamental causes of GI dysmotility.

scholarly journals Aqueous Extracts of Herba Cistanche Promoted Intestinal Motility in Loperamide-Induced Constipation Rats by Ameliorating the Interstitial Cells of Cajal

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Shuai Yan ◽  
Yin-zi Yue ◽  
Xiao-peng Wang ◽  
Hong-li Dong ◽  
Shu-guang Zhen ◽  
...  
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Colonic Motility ◽  
Functional Constipation ◽  
Serum Levels ◽  
Interstitial Cells ◽  
Slow Transit Constipation ◽  
Mrna Levels ◽  
Aqueous Extracts ◽  
Slow Transit ◽  
Cells Of Cajal

Traditional Chinese medicine was reported to have good effects in treating functional constipation. This work attempted to prove the effects of aqueous extracts of Herba Cistanche (AEHC) on STC treatment and to determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. HPLC was performed for identification and confirmation of the bioactive components in the AEHC. It was found that AEHC attenuated STC responses based on increased fecal quantity, moisture content, and intestinal transit rate, as well as serum levels of GAS, MTL, SS, and CGRP. The protein and mRNA levels of c-kit, a labeling of interstitial cells of Cajal (ICC), also increased. Meanwhile, only the protein level of SCF, a ligand of c-kit, increased. The analysis of our data suggested that AEHC could obviously improve the function of ICC via a signaling pathway involving PI3K, SCF, and c-kit and enhance colonic motility indices such as GAS, MTL, SS, and CGRP. It is interesting to note that AEHC appeared to be effective on constipation, so further experiments are necessary to clarify the exact mechanisms involved.

Sign in / Sign up

Export Citation Format

Share Document