Elevation of HO-1 Expression Mitigates Intestinal Ischemia-Reperfusion Injury and Restores Tight Junction Function in a Rat Liver Transplantation Model

Chi, Xinjin; Yao, Weifeng; Xia, Hua; Jin, Y.; Xi, Li; Cai, Jun

doi:10.1155/2015/986075

Cited by 85 publications

(50 citation statements)

References 48 publications

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“…HO-1 plays an important role in improving intestinal barrier function. In a rat liver transplantation model, elevation of HO-1 mitigates intestinal ischemia-reperfusion injury and restores TJ function (17), and serum endotoxin, D-Lac and DAO were significantly increased demonstrates this. The presence of bile in the gut is essential for the maintenance of intestinal mucosal barrier function; bile salt deficiency can lead to intestinal mucosal atrophy and intestinal mucosa barrier dysfunction (34).…”

Section: Ho-1 Increased Occludin and Inhibited Phospho-nf-jb P65 Protmentioning

confidence: 91%

“…Previous reports have shown that induction of HO-1 expression contributes to protection against liver damage in various liver diseases such as acute liver injury, alcoholic liver disease, liver fibrosis and ischemia/reperfusion injury (12)(13)(14)(15). Encouragingly, activation of HO-1 counteracts LPS-induced inflammatory and oxidative damage (16) and can also alleviate intestinal ischemia-reperfusion injury (17). Our previous study found that endogenous activation of HO-1 by cobalt protoporphyrin (CoPP) could suppress immune liver fibrosis (18), and another of our experiments showed that inhibiting HO-1 activity could be helpful in ameliorating BDL-induced liver cirrhosis (19).…”

Section: Introductionmentioning

confidence: 99%

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The Protective Effect of Heme Oxygenase-1 against Intestinal Barrier Dysfunction in Cholestatic Liver Injury Is Associated with NF-κB Inhibition

Zhang

Liu

et al. 2017

Mol Med

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Heme oxygenase-1 (HO-1) is reported to protect against liver injury, but little is known about its effect on the intestinal barrier in cholestatic liver injury. In this study, we investigated the effects of HO-1 and its enzymatic by-product on intestinal barrier dysfunction in bile duct ligation (BDL) rats and explored the possible mechanism. The HO-1 inducer cobalt protoporphyrin (CoPP) and carbon monoxide-releasing molecule-2 (CORM-2) were used; the expression levels of tight junction (TJ) proteins, intestinal inflammation and NF-κB p65 were measured. For an in vitro experiment, stable Caco-2 cell lines were constructed, one overexpressed the HO-1 gene and another with that gene knocked down, and the specific NF-κB inhibitor JSH-23 was used. CoPP and CORM-2 treatment alleviated liver and intestinal mucosa injury in BDL rats; improved ZO-1, claudin-1 and PCNA expression; and reduced cell apoptosis and intestinal interleukin-6 (IL-6) expression. In vitro studies confirmed that HO-1, ZO-1 and occludin were overexpressed in HO-1-transfected Caco-2 cells, while decreased in the short hairpin HO (sh-HO-1) group. JSH-23 significantly increased occludin expression in both the HO-1 overexpression and sh-HO-1 groups, compared with their respective controls. HO-1 overexpression also inhibited the nuclear translocation of NF-κB p65 after lipopolysaccharide (LPS) treatment. Additionally, phospho-p65 expression in sh-HO-1 cells was significantly increased compared with that of the HO-1 overexpression group. In conclusion, HO-1 and CORM-2 improved intestinal epithelial barrier function in BDL-induced cholestatic liver injury mainly by restoring TJ, reducing cell apoptosis and intestinal inflammation. HO-1 exerts a protective effect, which is partially correlated with the regulation of NF-κB.

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Section: Ho-1 Increased Occludin and Inhibited Phospho-nf-jb P65 Protmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

The Protective Effect of Heme Oxygenase-1 against Intestinal Barrier Dysfunction in Cholestatic Liver Injury Is Associated with NF-κB Inhibition

Zhang

Liu

et al. 2017

Mol Med

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“…Mice were killed at 24 hours after surgery. The dose/schedule selection for hemin and CrMP was based on literature.…”

Section: Methodsmentioning

confidence: 99%

“…13,48 In the present study, hemin was used in a dose of 30 mg kg -1 hemin ip as this dose was shown to counteract inflammation in different animal models. 22,25,38,45 As the time interval of administration of hemin before the inflammatory stimulus varied in these studies, we first investigated the HO-1 protein expression in intestinal muscular tissue at 6, 12, and 24 hours after administration of 30 mg kg -1 hemin ip in non-manipulated mice. This resulted in a time-dependent increase in HO-1 protein levels with the highest induction of HO-1 at 24 hours after administration of hemin.…”

Section: Investigation Of the Possible Role Of Nf-κb P65 In The Promentioning

confidence: 99%

Hemin reduces postoperative ileus in a heme oxygenase 1‐dependent manner while dimethyl fumarate does without heme oxygenase 1‐induction

Dingenen

Pieters

Nuffel

et al. 2019

Neurogastroenterology Motil

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Background Postoperative ileus (POI), the impairment of gastrointestinal motility after abdominal surgery, is mainly due to intestinal muscular inflammation. Carbon monoxide (CO)‐releasing compounds were shown to exert an anti‐inflammatory effect in murine POI partially through induction of heme oxygenase‐1 (HO‐1). The influence of hemin and dimethyl fumarate (DMF), currently used for multiple sclerosis (MS), was therefore tested in murine POI. Methods C57BL/6J mice were anesthetized and after laparotomy, POI was induced via intestinal manipulation (IM). Animals were treated with either 30 mg kg‐1 hemin intraperitoneally (ip), 30 mg kg‐1 DMF ip, or 100 mg kg‐1 intragastrically (ig) 24 hours before IM. Intestinal transit was assessed 24 hours postoperatively and mucosa‐free muscularis or whole segments of the small intestine were stored for later analysis. Intestinal HO‐1 protein expression was studied at 6, 12, and 24 hours after administration of hemin or DMF in non‐manipulated mice. Key results Pretreatment with hemin and DMF, both ig and ip, prevented the delayed transit seen after IM. Concomitantly, both hemin and DMF significantly reduced the increased interleukin‐6 levels and the elevated leukocyte infiltration in the muscularis. Hemin but not DMF caused a significant increase in intestinal HO‐1 protein expression and co‐administration of the HO‐1 inhibitor chromium mesoporphyrin abolished the protective effects of hemin on POI; DMF reduced the IM‐induced activation of NF‐κB and ERK 1/2. Conclusions and Inferences Both hemin and DMF improve the delayed transit and inflammation seen in murine POI, but only hemin does so in a HO‐1‐dependent manner.

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“…Five randomly selected fields (×200) were captured from each slide using a light microscope in a blinded manner. The severity of intestinal injury was graded by two histopathologists who were initially blind to the experiment based on the criteria of Chiu's method [18,19].…”

Section: Evaluation Of Histological Injurymentioning

confidence: 99%

MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline

et al. 2020

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Background: Hydrogen-rich saline (HRS) has been proven effective against ischemia/reperfusion (I/R) injury. However, knowledge on the underlying signaling events remain poor. Having recent highlight of microRNAs (miRNAs) in mediating intestinal I/R injury, we hypothesized that HRS may protect intestine against I/R injury by regulating miRNAs. Method: Mice were given intraperitoneal injection of saline or HRS once daily for five consecutive days before undergoing intestinal I/R that was induced by 60-min ischemia followed by 180-min reperfusion of superior mesenteric artery. The intestine was collected for histopathological assay, miRNA microarray profiling, Real-Time PCR, and Western blotting. Next, miR-199a-3p mimics or inhibitors were transfected into IEC-6 cells to explore the relationship between HRS treatment and miR-199a-3p. Results: I/R-induced mucosal injury and epithelial cells apoptosis were attenuated by HRS pretreatment. A total of 64 intestinal I/R-responsive miRNAs were altered significantly by HRS pretreatment, in which we validated four novel miRNAs with top significance by was drastically increased by I/R but reduced by HRS. Computational analysis predicts insulin-like growth factor (IGF)-1, mammalian target of rapamycin (mTOR), and phosphoinositide-3-kinase (PI3K) regulatory subunit 1 as targets of miR-199a-3p, suggesting involvement of the pro-survival pathway, IGF-1/PI3K/Akt/mTOR. In in vitro experiment, HRS treatment reduced miR-199a-3p level, increase IGF-1, PI3K and mTOR mRNA expression, restore IEC-6 cells viability, and this protective effects were reversed under miR-199a-3p mimics treatment. Conclusion: Collectively, miR-199a-3p may serve a key role in the anti-apoptotic mechanism of HRS that contributes to its protection of the intestine against I/R injury.

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Elevation of HO-1 Expression Mitigates Intestinal Ischemia-Reperfusion Injury and Restores Tight Junction Function in a Rat Liver Transplantation Model

Cited by 85 publications

References 48 publications

The Protective Effect of Heme Oxygenase-1 against Intestinal Barrier Dysfunction in Cholestatic Liver Injury Is Associated with NF-κB Inhibition

The Protective Effect of Heme Oxygenase-1 against Intestinal Barrier Dysfunction in Cholestatic Liver Injury Is Associated with NF-κB Inhibition

Hemin reduces postoperative ileus in a heme oxygenase 1‐dependent manner while dimethyl fumarate does without heme oxygenase 1‐induction

MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline

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