miR-1273g-3p participates in acute glucose fluctuation-induced autophagy, dysfunction, and proliferation attenuation in human umbilical vein endothelial cells

Abstract

-Acute glucose fluctuations (AGF) often cause high mortality among critically ill patients, but the mechanisms induced by AGF are not clear. Recent studies suggest that endothelial dysfunction is a key factor that leads to high mortality among critically ill patients. Our goal is to evaluate the phenomenon and mechanisms of endothelial dysfunction induced by AGF. In this study, the functions of human umbilical vein endothelial cells (HUVECs) were compared after treatment with sustained high glucose (SHG), AGF in two groups (AGF1 fluctuations between 5 and 16 mM and AGF2 fluctuations between 5 and 25 mM), and normal glucose levels as a control group (CTR). The medium of the groups was changed every 4 h. The influence of AGF on wound healing was also tested on C57BL/6 mice. The results show that cell proliferation, angiogenesis, and migration functions were injured in the SHG and both AGF groups. AGF2 group shows the worse condition in vitro. In vivo, the wound healing was delayed after the AGF treatment. Furthermore, the markers of apoptosis and autophagy were analyzed. We observed that the autophagy changed in all treatment groups, but apoptosis showed no change. To get to know the mechanism of dysfunction and autophagy, we performed the microRNA chip assay and real-time PCR and found miR-1273g-3p remarkably changed in AGF2 group. After the mimic and inhibitor of miR-1273g-3p were transfected during the AGF2 treatment, we found that the dysfunction and autophagy were partially enhanced by miR-1273g-3p mimic and reversed by miR-1273g-3p inhibitor in AGF2 group. Thus, we conclude that AGF can induce more dysfunction and autophagy, and miR-1273g-3p is also an important factor that leads to the injury. glucose fluctuations; endothelial dysfunction; wound healing; autophagy; miR-1273g-3pINCREASING GLYCEMIC VARIABILITY can greatly increase the risk of mortality among critically ill patients. Several previous studies suggest that the variability in glucose levels over time is an important determinant of mortality among critically ill patients (21,22,58). Alternatively, recent evidence shows that glucose fluctuations may influence the development of diabetic complications(4, 47) and may produce more serious injury in organ functions than sustained high blood glucose. Krinsley and Preiser (20) reported that if a blood glucose range of 70 -140 mg/dl is maintained for Ͼ80% of the time, the chances of survival of nondiabetic critically ill adults will be greatly increased. Organ injury induced by glucose toxicity is commonly observed in both intensive care units and endocrine departments. The damage is also observed in in vitro cell culture and animal studies. Therefore, some authors have proposed that "glycemic variability" is a new therapeutic challenge in diabetes and the critical care setting (7).The mechanism of the production of glucose fluctuations is variable in several studies (35)(36)(37)(38)(39)57) in both preclinical and clinical research studies. However, this is not appropriate for the critically ill patient...

Expression profile of circular RNAs in placentas of women with gestational diabetes mellitus

“…an miRNA in 2011 and can bind to 1,074 genes [30]. Guo et al [38] reported that miR-1273g-3p participates in acute glucose fluctuation and is an important factor that leads to endothelial dysfunction and autophagy. It is also involved in the progression of several complications caused by diabetes by modulating the autophagylysosome pathway and could serve as a new target for disease therapy [39].…”

miR‑1273g‑3p promotes proliferation, migration and invasion of LoVo cells via cannabinoid receptor 1 through activation of ERBB4/PIK3R3/mTOR/S6K2 signaling pathway

“…miR-1273g-3p, a length of 21 nt non-coding RNA molecule, is coded in an intron of the SCP2 gene, and was first discovered in 2011 years (7). Previous study has reported that miR-1273g-3p participates in acute glucose fluctuation-induced proliferation attenuation in human umbilical vein endothelial cells (8). And miR-1273g-3p could modulate activation and apoptosis of hepatic stellate cells by directly targeting PTEN in HCV-related liver fibrosis (9).…”

Plasma miR-1273g-3p acts as a potential biomarker for early Breast Ductal Cancer diagnosis

“…MiR-1273 consists of miR-1273amiR- , miR-1273cmiR- , miR-1273dmiR- , miR-1273e, miR-1273f, miR-1273g-3p, miR-1273g-5p, miR-1273h-3p and miR-1273h-5p (Ivashchenko et al 2014. Guo and his colleagues found that miR-1273g-3p participates in acute glucose fluctuation-induced autophagy, dysfunction, and proliferation attenuation in human umbilical vein endothelial cells (Guo et al 2016). Sahu and his colleagues found that miR-1273g-3p had a relationship with megakaryocyte differentiation (Sahu et al 2018).…”