The Role of Interstitial Cells of Cajal in Acute Cholecystitis in Guinea Pig Gallbladder

Huang, Zhenpeng; Qiu, Hu; Yang, Yan; Zhang, Li; Yang, Bin; Lin, Mengjuan; Yu, Baoping

doi:10.1159/000443116

Cited by 8 publications

(8 citation statements)

References 32 publications

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“…In AC, biliary tract obstruction leads to ICC injury in the gallbladder. This then blocks c-kit receptors, and results in gallbladder ICC loss, increased ICC apoptosis, and a lack of regeneration and maintenance of ICC networks [32,33]. c-kit receptors modulate the generation and rhythmicity of electrical activity to regulate the excitability of gallbladder smooth muscle cells [27].…”

Section: Discussionmentioning

confidence: 99%

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

Huang¹,

Qiu²,

Yu³

2018

Cell Physiol Biochem

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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.

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Section: Discussionmentioning

confidence: 99%

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

Huang¹,

Qiu²,

Yu³

2018

Cell Physiol Biochem

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“…Maintenance of ICCs requires SCF/c-kit signaling [ 8 ], which suggests that repressing this pathway can result in a decrease in the number of ICCs. This may lead to the development of many diseases such as acute cholecystitis [ 26 ], cholesterol gallstones [ 27 ], gastric dysmotility [ 28 ], diabetes-related voiding dysfunction [ 29 ], and diabetic gastroparesis [ 30 ]. However, there are no reports of investigations into whether the reduced ICC number in STC patients is associated with an inhibition of the SCF/c-kit signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Yangyin Runchang Decoction Improves Intestinal Motility in Mice with Atropine/Diphenoxylate‐Induced Slow‐Transit Constipation

Jiang

Zhou

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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This study assessed the efficacy and mechanism of action of Yangyin Runchang decoction (YRD) in the treatment of slow-transit constipation (STC). ICR mice were randomly divided into four groups (n = 10/group) and treated with saline (normal control; NC), atropine/diphenoxylate (model control; MC; 20 mg/kg), or atropine/diphenoxylate plus low-dose YRD (L-YRD; 29.6 g/kg) or high-dose YRD (H-YRD; 59.2 g/kg). Intestinal motility was assessed by evaluating feces and the intestinal transit rate (ITR). The serum level of stem cell factor (SCF) and changes in interstitial cells of Cajal (ICCs) were also evaluated. Additionally, the expression of SCF and c-kit and the intracellular Ca2+ concentration [Ca2+]I were investigated. Fecal volume and ITR were greater in the L-YRD and H-YRD groups than in the MC group. The serum SCF level was lower in the MC group than in the NC group; this effect was ameliorated in the YRD-treated mice. Additionally, YRD-treated mice had more ICCs and elevated expression of c-kit and membrane-bound SCF, and YRD also increased [Ca2+]I in vitro in isolated ICCs. YRD treatment in this STC mouse model was effective, possibly via the restoration of the SCF/c-kit pathway, increase in the ICC count, and enhancement of ICC function by increasing [Ca2+]i.

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“…The adult guinea pigs were randomly divided into four groups: Control group, 24 hr common bile duct ligation (CBDL) group, 48-hr CBDL group, and antipolymorphonuclear neutrophil (PMN) group. CBDL was performed in the last three groups to induce acute cholecystitis as previously described (Huang, Qiu, Yang, Zhang, et al, 2016). Briefly, the common bile duct was bluntly separated and ligated with 5-0 surgical sutures.…”

Section: Animalsmentioning

confidence: 99%

“…CBDL was performed in the last three groups to induce acute cholecystitis as previously described (Huang, Qiu, Yang, Zhang, et al, 2016). Briefly, the common bile duct was bluntly separated and ligated with 5-0 surgical sutures.…”

Section: Animalsmentioning

confidence: 99%

“…It is induced by many factors, including gallstones, chemical injury, and other diseases (Ambe, Papadakis, & Zirngibl, 2016). In a recent study (Huang, Qiu, Yang, Zhang, et al, 2016), we noticed that the density of gallbladder ICLCs was significantly decreased in acute cholecystitis, a change that is attributed to the downregulation of stem cell factor (SCF) and mast-stem cell growth factor receptor (c-kit). These data offer a preliminary explanation for the observed gallbladder dysmotility.…”

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confidence: 99%

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Neutrophils injure gallbladder interstitial Cajal‐like cells in a guinea pig model of acute cholecystitis

Lin

Chen

Huang

et al. 2018

Journal Cellular Physiology

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Acute cholecystitis is a common disease with gallbladder dysmotility. Disease pathogenesis involves immune cell infiltration as well as changes in gallbladder interstitial Cajal-like cells (ICLCs). However, it remains unclear if or how the immune cells affect ICLC morphology, density, distribution, and function in gallbladder tissue during acute cholecystitis. In this study, we explored the acute cholecystitis-related alterations in gallbladder ICLCs in a guinea pig model, focusing on the effects of neighboring neutrophils. Adult guinea pigs were randomly divided into four groups (control, 24 hr common bile duct ligation [CBDL], 48-hr CBDL, and antipolymorphonuclear neutrophil[PMN] treated) and analyzed using methylene blue staining and immunofluorescence.Gallbladder contractility was also monitored. To culture gallbladder ICLCs, collagenase digestion was performed on tissue from 10-to 15-day-old guinea pigs. Neutrophils isolated from the peripheral blood of experimental animals 48-hr postsurgery were also cocultured with the gallbladder ICLCs. Intracellular calcium was detected with Fluo-4 AM dye. Our results showed that gallbladder ICLC density significantly declined during acute cholecystitis and was accompanied by shortening of the cellular processes and damage to their network-like structure. However, pretreatment with anti-PMN partially prevented these changes. Gallbladder contraction was also significantly decreased during acute cholecystitis, and this appeared to be mediated by the neutrophils. Moreover, ICLCs cocultured with neutrophils also had shortened and reduced processes and impaired network-like structure formation. Intracellular calcium transient was less sensitive to contraction agonists and inhibitors when cocultured with neutrophils. Taken together, neutrophils greatly affect gallbladder ICLCs and dysmotility during acute cholecystitis.

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The Role of Interstitial Cells of Cajal in Acute Cholecystitis in Guinea Pig Gallbladder

Cited by 8 publications

References 32 publications

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

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

Yangyin Runchang Decoction Improves Intestinal Motility in Mice with Atropine/Diphenoxylate‐Induced Slow‐Transit Constipation

Neutrophils injure gallbladder interstitial Cajal‐like cells in a guinea pig model of acute cholecystitis

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