Low expression of microRNA-328 can predict sepsis and alleviate sepsis-induced cardiac dysfunction and inflammatory response

Sepsis often leads to cardiac dysfunction and inflammation. This study investigated the clinical value of microRNA-328 (miR-328) in sepsis and its role in cardiac dysfunction and inflammation caused by sepsis. The expression level of miR-328 in the serum of the subjects was detected by qRT-PCR. Receiver operating characteristic (ROC) curve measured the diagnostic value of miR-328 in sepsis. Rat sepsis model was established to detect left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal rate of increase/decrease of left ventricular pressure (±dp/dtmax). Myocardial injury markers serum cardiac troponin I (cTnI), myocardial kinase isoenzyme (CK-MB), and inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). miR-328 expression was assessed in serum of sepsis patients and in rat models of sepsis. The AUC of ROC curve was 0.926, sensitivity 87.60%, and specificity 86.36%. Compared with the sham group, LVSP and +dp/dtmax were decreased in the rat model of sepsis. LVEDP, -dp/dtmax, cTnI, CK-MB, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β were upregulated in the rat model of sepsis. The low expression of miR-328 reversed these indicators. miR-328 is a diagnostic marker for patients with sepsis, and decreasing the expression level of miR-328 can ameliorate cardiac dysfunction and cardiac inflammation in sepsis.

Regulation and its signaling mechanism of miR-328on endothelial-mesenchymal transition induced by high glucose of humanumbilical vein endothelial cells / 基础医学与临床

Objective The study is to investigate the role of miR-328 in endothelial mesenchymal transition (EMT)induced by high glucose in human umbilical vein endothelial cells (HUVECs)and its signaling mechanism.Methods HUVECs were cultured in high glucose environment to induce EMT;The recombinant lentiviruses were created by miR-328 and antagomiR- 328 transfection of HUVECs.The experiment was divided into seven groups: normal glucose;mannitol group;high glucose;miR-328;miR-328 virus negative control;high glucose + U0126;miR-328 + U0126.Double immunofluorescent staining was used to determine expression of EMT markers;Changes in miR-328 expression is examined by RT-qPCR;The expressions of type Ⅰ/Ⅲ collagen,p-MEK1/2 and p-ERK1/2 are examined by Western blot.Results 1)HUVECs showed positive staining for CD31 and α-SMA in high glucose group.2)The expression of miR-328 was up-regulated(P<0.05)in HUVECs treated by high glucose or miR-328.Compared with high glucose group or miR-328 group,miR-328 expression was less pronounced aftertreatment with U0126.3)The expressions of type Ⅰ/Ⅲ collagen increased in HUVECs treated by high glucose or miR-328(P<0.05) Compared with high glucose group or miR-328 group,typeⅠ/Ⅲ collagen expressions were less pronounced after treatment with U0126.4)The expressions of p-MEK1/2 and p-ERK1/2 were increased in HUVECs treated by high glucose or miR-328 in comparison to the control group (P<0.05);a lower expression of p-MEK1/2 and p-ERK1/2 were observed in U0126 group than in high glucose group or miR-328 group.Conclusions The phenomenon of EMT in HUVECs is induced by high glucose with increased expression of miR-328;overexpression of miR-328 induced EMT in HUVECs;miR-328 induced EMT is related with MEK1/2-ERK1/2 signaling pathway.