Dysregulation of microRNA biogenesis in the small intestine after ethanol and burn injury

Abstract

Ethanol exposure at the time of burn injury is a major contributor to post-burn pathogenesis. Many of the adverse effects associated with ethanol and burn injury are linked to an impaired intestinal barrier. The combined insult causes intestinal inflammation, resulting in tissue damage, altered tight junction expression, and increased intestinal permeability. microRNAs play a critical role in maintaining intestinal homeostasis including intestinal inflammation and barrier function. Specifically, miR-150 regulates inflammatory mediators which can contribute to gut barrier disruption. The present study examined whether ethanol and burn injury alters expression of microRNA processing enzymes (Drosha, Dicer, and Argonaute-2) and miR-150 in the small intestine. Male mice were gavaged with ethanol (~2.9g/kg) 4 hours prior to receiving a ~12.5% total body surface area full thickness burn. One or three days after injury, mice were euthanized and small intestinal epithelial cells (IECs) were isolated and analyzed for expression of microRNA biogenesis components and miR-150. Dicer mRNA and protein levels were not changed following the combined insult. Drosha and Argonaute-2 mRNA and protein levels were significantly reduced in IECs one day after injury; which accompanied reduced miR-150 expression. To further determine the role of miR-150 in intestinal inflammation, young adult mouse colonocytes were transfected with a miR-150 plasmid and stimulated with LPS (100ng/mL). miR-150 overexpression significantly reduced IL-6 and KC protein levels compared to vector control cells challenged with LPS. These results suggest that altered microRNA biogenesis and associated decrease in miR-150 likely contributes to increased intestinal inflammation following ethanol and burn injury.

Edaravone reduces oxidative stress and intestinal cell apoptosis after burn through up-regulating miR-320 expression

“…MicroRNAs (miRNAs) are short non-coding RNA sequences that play critical roles in a variety of physiological and pathological processes (Fromm et al, 2015). Burn injury, disease and some other factors could change the expressions of miRNAs and therefore negatively affect intestinal homeostasis (Morris et al, 2017). MiR-320 is a member of the miRNAs (Song et al, 2014), to date, evidence demonstrated that miR-320 was involved in a variety of pathological processes, including myocardial ischemia reperfusion injury, and it is associated with cell proliferation, apoptosis and death (Zhang et al, 2016) .…”

Protective effects of PX478 on gut barrier in a mouse model of ethanol and burn injury

“…Altered expressions of miRs have been associated with altered intestinal barrier function affecting components such as tight junction protein and mucins. In particular, miR-150 has been shown to have a role in mediating inflammation, [20][21][22] which is a major adverse effect following the combined insult of ethanol and burn injury. 11,12 Similarly, other miRs such as miR-7a have roles in regulating components of the intestinal barrier such as inflammation.…”

Role of HIF-1α in Alcohol-Mediated Multiple Organ Dysfunction

“…Numerous studies demonstrate that alcohol exacerbates adverse effects to the gut following injury and disease [82,87,91,92,93]. In a two-hit model of co-exposure of colon cancer cell lines to alcohol and/or arsenic, alcohol or arsenic alone increased ROS production; however, there were additive effects when alcohol and arsenic exposure were combined.…”