Regulatory role of microRNA-30b and plasminogen activator inhibitor-1 in the pathogenesis of cognitive impairment

Abstract

Abstract. The present study aimed to investigate the role of plasminogen activator inhibitor-1 (PAI-1) in drug-induced early cognitive impairment and the underlying mechanism concerning microRNA (miR)-30b. A mouse model of cognitive impairment was established by intraperitoneal injection of scopolamine (2 mg/kg body weight) for 13 days. Behavioral performance was assessed using the Morris water maze (MWM) test. The mRNA expression levels of PAI-1 and miR-30b were detected using quantitative polymerase chain reaction (qPCR). The protein expression levels of PAI-1 in the hippocampus and blood were determined using western blot analysis and enzyme-linked immunosorbent assays. The MWM test demonstrated that, on days 3 and 4, the escape latency was significantly elevated in the model mice in comparison with control group (P<0.05). In addition, the length of swimming path was significantly increased (P<0.05), while the number of times of crossing the platform location was significantly reduced in the model mouse group (P<0.05) in comparison with the control group. qPCR demonstrated that the mRNA expression levels of PAI-1 in the model mice was significantly elevated in the hippocampus and blood in comparison with the control group (P<0.01). Furthermore, western blot analysis and enzyme-linked immunosorbent assay demonstrated that the protein expression levels of PAI-1 were significantly elevated in the hippocampus and blood in the model group, in comparison with the control group (P<0.05). Notably, the levels of miR-30b in the hippocampus and blood were significantly decreased in the model mice in comparison with the control group (P<0.01). To conclude, the expression levels of PAI-1 were significantly elevated in mice with scopolamine-induced cognitive impairment, which may be associated with the downregulation of miR-30b. The findings from the present study suggest that miR-30b may be involved in the regulation of PAI-1, which would contribute to the pathogenesis of cognitive impairment.

Retracted: MicroRNA‐335‐5p suppresses lower extremity deep venous thrombosis by targeted inhibition of PAI‐1 via the TLR4 signalingpathway

“…44 Through analysis with CCK-8 and flow cytometry, augmented proliferation and attenuated apoptosis were determined in femoral vein endothelial cells when miR-335-5p expression was up-regulated and PAI-1 expression was down-regulated. MiR-335-5p has been reported to be involved in cell differentiation and apoptosis of osteoblasts in diabetic osteoporosis, 47 In addition, miR-335 has the ability to influence apoptosis and invasion in non-small cell lung cancer, 48 and clear cell renal cell cancer proliferation and invasion by inhibiting the expression of BCL-W. 49 Meanwhile, PAI-1 is proved to be an apoptosis-related biomarker in predicting the efficacy of neoadjuvant chemotherapy in the study of Fersching et al 50 Specifically, apoptosis inducted by PAI-1 in vascular cells is associated with anti-adhesive characteristics via the caspase 3 signaling pathway, which is demonstrated in the report of Al-Fakhri et al 51 Furthermore, compared with the blank and siRNA-NC groups, the length and weight of thrombus were decreased in both the miR-335-5p mimics and siRNA-PAI-1 groups. Bonemarrow-derived endothelial progenitor cells (EPCs) play an important role in the new vessel formation.…”

Non-Coding RNA as Novel Players in the Pathophysiology of Schizophrenia

“…Additionally, miR-30B levels in these subjects are correlated with the genotype of the rs2234693 SNP in the estrogen receptor- α gene ( ESR1 ). Furthermore, females with schizophrenia have less severe deficits in cognitive parameters, such as memory, compared to males [ 143 ], and both miR-30B and ESR1 have been shown to be important for cognitive function [ 144 , 145 , 146 , 147 ]. Thus, miR-30B warrants further study to understand whether it may be protective against cognitive deficits seen in schizophrenia.…”

MicroRNA‑30b protects myocardial cell function in patients with acute myocardial ischemia by targeting plasminogen activator inhibitor‑1

“…Singh et al (46) reported that miR-200c directly regulates the expression of dual specificity protein phosphatase 1, downregulates the activity of the mitogen-activated protein kinase signaling pathway and promotes cardiomyocyte hypertrophy. Based on the results of a study investigating the regulation of PAI-1 by miRNA (47), the present study used bioinformatics to identify the miRNA that regulates PAI-1 expression; the results indicated that miR-30b regulates PAI-1. Previous studies have demonstrated that miR-30b affects the Figure 7.…”