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

Abstract

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.

Hydrogen: A Novel Option in Human Disease Treatment

“…Wang et al interestingly discovered that cytotoxin-associated gene A cytotoxin, a virulence factor of Helicobacter pylori that augments the risk of gastric cancer, can be delivered into host cells by the H 2 -utilizing respiratory chain of the bacterium, extending the roles of H 2 oxidation to include transport of a carcinogenic toxin [ 124 ]. Although this study indicated that H 2 may play a role in increasing gastric cancer risk, abundant studies also demonstrated that H 2 is protective in gastric damage induced by oxidative stress [ 125 ] and aspirin [ 126 ].…”

Hydrogen-rich saline protects intestinal epithelial tight junction barrier in rats with intestinal ischemia–reperfusion injury by inhibiting endoplasmic reticulum stress-induced apoptosis pathway

“…Hydrogen, once thought to have no biological effects, has begun to receive widespread attention and research. It has been found that hydrogen plays an important protective role in multiple disease models and multiple clinical trials [37,38], especially in alleviating acute IRI in organs such as intestine [22,39,40], heart [41], liver and kidney [42]. These studies demonstrate that hydrogen can reduce IRI through antioxidant, anti-inflammatory, and other mechanisms.…”

Intestinal Epithelial Cell Derived Exosomes Package MicroRNA-23a-3p Alleviate Gut Damage After Ischemia/Reperfusion via Targeting MAP4K4

“…MiR-23a-5p [27], miR-21 [29] miR-182 [34] and miR-199a-3p [35] upregulate while miR-29b-3p downregulates [30] in underlying II/R insult. Upregulation of miR-199a-3p dramatically decreased insulin-like growth factor-1, mTOR, and phosphoinositide-3-kinase regulatory subunit 1 protein expression as target genes of miR-199a-3p following II/R damage [35]. MiR-146a is a key regulator of the apoptosis of intestinal epithelial cells during I/R insult through TLR4/NF-κB pathway [27].…”

“…MiRNAs have been reported to be related to apotosis, in ammation, autophay, oxidative stress, and intestinal barrier dysfunction after IIR injury [26][27]. MiRNAs including miR-23a-5p, miR-146a, miR-21, miR-29b-3p, miR-381-p, miR-351-5p, miR-34a-5p, miR-665-3p, miR-682, miR-182 and miR-199a-3p have been involved in modulating mucosal damage following I/R damage in small intestines [27][28][29][30][31][32][33][34][35][36]. MiR-23a-5p [27], miR-21 [29] miR-182 [34] and miR-199a-3p [35] upregulate while miR-29b-3p downregulates [30] in underlying II/R insult.…”