Cellular mechanism of mechanotranscription in colonic smooth muscle cells

Li, Feng; Lin, You Min; Sarna, Sushil K.; Shi, Xuan–Zheng

doi:10.1152/ajpgi.00440.2011

Cited by 23 publications

(81 citation statements)

References 42 publications

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“…Consistent with previous findings 1,29,30 , colonic smooth muscle contractile response was dramatically suppressed in OB. However, antibiotic treatment did not improve colon muscle contractility in OB (Fig.…”

Section: Resultssupporting

confidence: 93%

Microbiota dysbiosis and its pathophysiological significance in bowel obstruction

Hegde

Lin

Golovko

et al. 2018

Sci Rep

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Bowel obstruction (OB) causes local and systemic dysfunctions. Here we investigated whether obstruction leads to alterations in microbiota community composition and total abundance, and if so whether these changes contribute to dysfunctions in OB. Partial colon obstruction was maintained in rats for 7 days. The mid colon and its intraluminal feces - proximal to the obstruction - were studied. OB did not cause bacterial overgrowth or mucosa inflammation, but induced profound changes in fecal microbiota composition and diversity. At the phylum level, the 16S rRNA sequencing showed a significant decrease in the relative abundance of Firmicutes with corresponding increases in Proteobacteria and Bacteroidetes in OB compared with sham controls. Daily treatment using broad spectrum antibiotics dramatically reduced total bacterial abundance, but increased the relative presence of Proteobacteria. Antibiotics eliminated viable bacteria in the spleen and liver, but not in the mesentery lymph node in OB. Although antibiotic treatment decreased muscle contractility in sham rats, it had little effect on OB-associated suppression of muscle contractility or inflammatory changes in the muscle layer. In conclusion, obstruction leads to marked dysbiosis in the colon. Antibiotic eradication of microbiota had limited effects on obstruction-associated changes in inflammation, motility, or bacterial translocation.

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Section: Resultssupporting

confidence: 93%

Microbiota dysbiosis and its pathophysiological significance in bowel obstruction

Hegde

Lin

Golovko

et al. 2018

Sci Rep

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“…The serosa and mucosa were removed and the remaining muscularis was cut into pieces [15]. The tissue was placed in a centrifuge tube containing a tissue digestion mixture of 0.1% collagenase type II (GIBCO) and 0.01% soybean trypsin inhibitor in Dulbecco's modified Eagle's medium (DMEM, GIBCO) for 20 min at 37°C [16], centrifuged for 5 min, and then the supernatant was removed. The cell pellet obtained was resuspended and stored at 37°C in DMEM containing 100 U/ml penicillin, 100 μg/ml streptomycin (P/S), and 10% fetal bovine serum (FBS).…”

Section: Methodsmentioning

confidence: 99%

Estrogen Regulates the Expression of Small-Conductance Ca<sup>2+</sup>-Activated K<sup>+</sup> Channels in Colonic Smooth Muscle Cells

et al. 2015

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Aim: This study aimed to determine the effects of small-conductance Ca²⁺-activated K⁺ (SK) channels in colonic relaxation and the regulation of SK channels by estrogen. Methods: The contractile activity of muscle strips from male rats was estimated, and drugs including vehicle (DMSO), 17β-estradiol (E2), or apamin (SK blocker) were added, respectively. In a further experiment, muscle strips were preincubated with apamin before exposure to E2. The levels of the SK2 and SK3 protein expression in the colonic smooth muscle cells (SMCs) were detected. SMCs were treated with ICI 182780 (estrogen receptor [ER] antagonist) plus E2, BSA-E2, PPT (ERα agonist), or DPN (ERβ agonist). SK3 mRNA and protein expression levels were detected. Results: The muscle strips responded to E2 with a decrease and to apamin with a transient increase in tension. Preincubation with apamin partially prevented E2-induced relaxation. Two SK channel subtypes, SK2 and SK3, were coexpressed with α-actin in colonic SMCs. The quantitative ratio of the SK transcriptional expression in colonic SMCs was SK3 > SK2. The SK3 expression was upregulated by E2, and was downregulated by ICI 182780, but was not influenced by BSA-E2. Furthermore, the effect of PPT on the expression of SK3 was almost the same as that of E2, while DPN did not influence the protein expression of SK3. Conclusion: These findings indicate that SK3 is involved in the E2-induced relaxing effect on rat colonic smooth muscle. Furthermore, E2 upregulates the expression of SK3 in rat SMCs, and that this effect is mediated via the ERα receptor.

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“…On the other hand, MCP-1 is a potent chemoattractant with an action of recruiting lymphocytes, monocytes and other inflammatory cells into the local site of the gut wall [2], [46], [47]. Our previous studies demonstrated that gene expression of COX-2 is markedly induced by mechanical stress in gut smooth muscle cells [25], [30]. COX-2 –derived PGs (i.e.…”

Section: Discussionmentioning

confidence: 99%

Mechanical Stress Is a Pro-Inflammatory Stimulus in the Gut: In Vitro, In Vivo and Ex Vivo Evidence

Lin

Shi

2014

PLoS ONE

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AimsInflammatory infiltrates and pro-inflammatory mediators are found increased in obstructive and functional bowel disorders, in which lumen distention is present. However, what caused the low level inflammation is not well known. We tested the hypothesis that lumen distention- associated mechanical stress may induce expression of specific inflammatory mediators in gut smooth muscle.MethodsStatic mechanical stretch (18% elongation) was applied in vitro in primary culture of rat colonic circular smooth muscle cells (RCCSMCs) with a Flexercell FX-4000 Tension Plus System. Mechanical distention in vivo was induced in rats with an obstruction band placed in the distal colon.ResultsIn the primary culture of RCCSMCs, we found that static stretch significantly induced mRNA expression of iNOS, IL-6, and MCP-1 in 3 hours by 6.0(±1.4), 2.5(±0.5), and 2.2(±0.5) fold (n = 6∼8, p<0.05), respectively. However, gene expression of TNF-α, IL-1β, and IL-8 was not significantly affected by mechanical stretch. In the in vivo model of colon obstruction, we found that gene expression of iNOS, IL-6, and MCP-1 is also significantly increased in a time-dependent manner in the mechanically distended proximal segment, but not in the sham controls or distal segments. The conditioned medium from the muscle strips of the stretched proximal segment, but not the distal segment or control, significantly induced translocation and phosphorylation of NF-κB p65. This treatment further increased mRNA expression of inflammatory mediators in the naïve cells. However, treatment of the conditioned medium from the proximal segment with neutralizing antibody against rat IL-6 significantly attenuated the activation of NF-κB and gene expression of inflammatory mediators.ConclusionsOur studies demonstrate that mechanical stress induces gene expression of inflammatory mediators i.e. iNOS, IL-6, and MCP-1 in colonic SMC. Further ex vivo study showed that mechanical stress functions as a pro-inflammatory stimulus in the gut.

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Cellular mechanism of mechanotranscription in colonic smooth muscle cells

Cited by 23 publications

References 42 publications

Microbiota dysbiosis and its pathophysiological significance in bowel obstruction

Microbiota dysbiosis and its pathophysiological significance in bowel obstruction

Estrogen Regulates the Expression of Small-Conductance Ca<sup>2+</sup>-Activated K<sup>+</sup> Channels in Colonic Smooth Muscle Cells

Mechanical Stress Is a Pro-Inflammatory Stimulus in the Gut: In Vitro, In Vivo and Ex Vivo Evidence

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