scholarly journals Herb-Partitioned Moxibustion Improves Crohn’s Disease-Associated Intestinal Fibrosis by Suppressing the RhoA/ROCK1/MLC Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Min Zhao ◽  
Zhijun Weng ◽  
Yan Huang ◽  
Handan Zheng ◽  
Dong Han ◽  
...  

Background and Aims. Intestinal fibrosis is one of the severe and common complications of Crohn’s disease (CD), but the etiology and pathogenesis remain uncertain. The study intended to examine whether the effect of herb-partitioned moxibustion on rats with CD-associated intestinal fibrosis is associated with the RhoA/ROCK1/MLC pathway. Methods. All experimental rats were randomly allocated into the normal control group (NC), model control group (MC), and herb-partitioned moxibustion group (HPM). Intestinal fibrosis was established in rats with CD by repeated rectal administrations of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Herb-partitioned moxibustion was applied at the Qihai (CV6) and Tianshu (ST25) acupoints once daily for 10 days in the HPM group. In this study, histological changes were examined by hematoxylin and eosin (HE) staining; then, Masson’s trichrome staining was used to assess the degree of fibrosis in each group. Experimental methods of immunohistochemistry, western blotting, and real-time PCR were applied to detect the levels of α-SMA, collagen III, RhoA, ROCK1, and p-MLC. Moreover, the double immunofluorescent staining for the colocalization of both α-SMA and ROCK1 was performed. Results. Contrasted with the normal controls, the collagen deposition and fibrosis scores were increased in colonic tissue of model rats, and HPM decreased the collagen deposition and fibrosis scores. The protein of α-SMA and collagen III in the MC group exceeds that of the NC group; HPM decreased the expression of α-SMA and collagen III in rats with intestinal fibrosis. Similarly, the expression of RhoA, ROCK1, and p-MLC in model rats was obviously increased compared with normal controls; the expression of RhoA, ROCK1, and p-MLC was decreased after HPM. The coexpression of α-SMA and ROCK1 in rats with intestinal fibrosis was higher than normal rats. Conclusion. HPM improves CD-associated intestinal fibrosis by suppressing the RhoA/ROCK1/MLC pathway.

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaomei Wang ◽  
Yuan Lu ◽  
Luyi Wu ◽  
Chen Zhao ◽  
Chunbin Song ◽  
...  

Intestinal fibrosis is the main pathological process in Crohn’s disease (CD); acupuncture and moxibustion can inhibit the process of fibrosis in CD rats, but the regulatory mechanism remains unknown. The present study observed the effect of moxibustion on the extracellular signal-regulated kinase (ERK) signaling pathway in the CD rat. The result shows that the phosphorylation of the Ras, Raf-1, MEK-1, and ERK-1/2 proteins and the expression of the corresponding mRNAs in the colon tissue of CD rat were significantly higher than the normal control group. Both treatments with mild moxibustion and with herb-separated moxibustion significantly reduced the expression of the Ras, Raf-1, MEK-1, and ERK-1/2 proteins and Ras and Raf-1 mRNA. MEK-1 and ERK-1/2 mRNA expression in each treatment group showed a downward trend, and the ERK-1/2 mRNA levels were significantly lower in the mild moxibustion group. It indicates that Ras, Raf-1, MEK-1, and ERK-1/2 are involved in the process of intestinal fibrosis in CD rats. Moxibustion can downregulate the abnormal expression of colonic Ras, Raf-1, MEK-1, and ERK-1/2 protein and mRNA levels in CD intestinal fibrosis in rats. Moxibustion may play a role in the treatment of CD intestinal fibrosis by regulating ERK signaling pathway.


2008 ◽  
Vol 24 (2) ◽  
pp. 111-117 ◽  
Author(s):  
N. Rodríguez-Pérez ◽  
A. Aguinaga-Barrilero ◽  
Marina B. Gorroño-Echebarría ◽  
Mercedes Pérez-Blas ◽  
J. M. Martín-Villa

We wished to analyse the frequency of Crohn’s disease-linked CARD15 polymorphisms (P268S, R702W, G908R and 1007fs) in a group of Spanish patients with idiopathic uveitis. To this aim, DNA samples were obtained from 111 unrelated patients. P268S, R702W and G908R polymorphisms were detected using TaqMan Genotyping kits (Applied Biosystems), and the 1007fs variation by direct DNA sequencing. Control group consisted of 105 healthy subjects.None of the polymorphisms studied revealed a significant increase in the groups of patients, when compared to the control group. Thus, P268S is found in 50% of patients (gene frequency 0.284) vs 44% of control individuals (gene frequency 0.245); R702W in 7% of patients (0.036) vs 7% (0.033); G908R in 2% of patients (0.009) vs 4% (0.019) and, finally, 1007fsin 2% of uveitis patients (0.008) vs 4% (0.021). Moreover, DNA sequencing has allowed us to define two new intronic polymorphisms in phase, in the 5' and 3' boundaries of the exon 11 (GenBank accession number #DQ 869189).Altogether, our results suggest that the Crohn’s disease-linked CARD15 polymorphisms do not seem to predispose to idiopathic uveitis in the Spanish population.


1989 ◽  
Vol 14 (1) ◽  
pp. 81-90 ◽  
Author(s):  
A. BOSMA ◽  
S. G. M. MEUWISSEN ◽  
B. H. CH. STRICKER ◽  
A. BROUWER

1977 ◽  
Vol 30 (11) ◽  
pp. 1063-1067 ◽  
Author(s):  
C F Culling ◽  
P E Reid ◽  
W L Dunn ◽  
M G Clay

2011 ◽  
Vol 140 (5) ◽  
pp. S-493 ◽  
Author(s):  
Yusuke Honzawa ◽  
Hiroshi Nakase ◽  
Kayoko Matsumura ◽  
Shuji Yamamoto ◽  
Norimitsu Uza ◽  
...  

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S161-S161
Author(s):  
I Georgopoulos ◽  
E Mavrigiannaki ◽  
S Stasinopoulou ◽  
G Renieris ◽  
G NIkolakis ◽  
...  

Abstract Background In the majority of patients, the areas of the intestine affected in Crohn’s disease (CD) are the terminal ileum and less commonly the rectum. The terminal ileum is affected in the majority of genetic animal models of CD as well. Additionally, CD recurs at sites of tight anastomosis or strictures postoperatively. These observations lead to the assumption that increased intraluminal pressure related to the presence of a valve, sphincter or stenosis is associated with CD pathogenesis. We investigated the hypothesis that the creation of a partial intestinal stenosis could have an impact on disease severity, in a genetic animal model of CD (TNFΔare/+). TNFΔare/+ mice overexpress TNFα leading to a Crohn-like colitis in the terminal ileum. Methods Twenty-nine TNFΔare/+ mice, 6 weeks old, were divided into three intervention groups: stenosis, sham and control. In the stenosis group (n = 11), a partial small bowel obstruction was created via a novel triple suture technique, approximately 3 cm from the ileocecal valve. In the control group (n = 9), a loose single suture was placed at the aforementioned site to test the direct effect of the foreign material on the intestinal wall. The sham group (n = 9) received a sham operation. The triple suture stenosis was also performed on wild-type (WT) C57BL/6 mice (group WT, n = 9). 6 weeks post-surgery all animals were sacrificed and samples from the ileum 3 cm proximal and 3 cm distal to the intervention site were collected for histopathological evaluation. The Crohn-like changes were assessed using a modified colitis histological scoring system (based on Katakura et al., JCI 2005; 115: 695–702). Results Proximal to the intervention, the mean colitis score of stenosis group (10.18 ± 0.87) was significantly higher compared with sham (6.33 ± 0.97, p: 0.009) and control group (5.00 ± 0.91, p: 0.001). There was no difference between sham and control group (p: 0.332). No significant differences between the groups were reported distal to the intervention. The triple suture technique led to Crohn-like inflammatory lesions only in the TNFΔare/+ mice, as shown from the significantly increased score compared with WT mice proximal and distal to the stenosis (10.18 ± 0.87 vs. 0.67 ± 0.37, p < 0.001 and 9.20 ± 1.09 vs. 0.33 ± 0.24, p < 0.001). Conclusion The creation of a stenotic segment in the intestine of TNFΔare/+ mice, led to higher colitis score than expected. The probable mechanism is the increased intraluminal pressure proximal to the stenosis. This suggests that mechanical forces contribute as important co-factors in the pathophysiology of CD, in genetically predisposed populations.


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